Search PubMed⌕ Search

Biomedical subjects

R Mattern

Publications and source records attributed to R Mattern.

At least 19 recordsLinked to original sources
PubMed2001

Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease.

OBJECTIVE: To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). DESIGN: Placebo-controlled, double-blind crossover trial in 22 patients with genetically confirmed SCA3/MJD. Study phases of 6 months were separated by a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice daily for 5.5 months. SETTING: Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany. MAIN OUTCOME MEASURES: Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the visual system were studied using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination. Physical and mental health were documented using the Medical Outcomes Study 36-Item Short-Form Health Survey. Subgroup analyses assessed the influence of age, sex, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance. RESULTS: Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimethoprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patients in the short-term analysis (2 weeks) or in the long-term interval (6 months). CONCLUSIONS: In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-sulfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.

Adult↗
PubMed2001

Saliva testing after single and chronic administration of dihydrocodeine.

In the present study, concentrations of dihydrocodeine and its metabolites in saliva and serum were compared after single low-dose and chronic high-dosage administration of the drug. In the first investigation, blood and saliva were collected periodically from six subjects after oral administration of 60 mg dihydrocodeine. In the second study, 20 subjects on oral dihydrocodeine maintenance provided single samples of blood and saliva simultaneously. Serum protein binding of salivary analytes and their recovery from the adsorbing material of the collection device as well as pH values of saliva samples were determined. The fluids were analyzed for dihydrocodeine and the major metabolites by high-performance liquid chromatography. In the single dose study dihydrocodeine was the only analyte found in saliva for up to 12-24 h post-dose. The half-life of dihydrocodeine in saliva was about twice that found in blood. The ratios of saliva/serum concentrations ranged from 1.2 to 17.0. After chronic high-dosage use, dihydrocodeine was the main salivary analyte and N-nordihydrocodeine was present in a few samples. Saliva/serum concentration ratios of dihydrocodeine were strongly dependent on the pH value of saliva and, to a lesser extent, on serum-protein binding. The saliva/serum ratios were more similar after chronic administration. The data suggest a passive diffusion process as the underlying mechanism for the transport of dihydrocodeine into saliva. After both single and chronic use, the presence of the drug in saliva can be used as evidence of recent substance administration.

Biotransformation↗
PubMed2001

In vitro stability of cocaine in whole blood and plasma including ecgonine as a target analyte.

The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4 degreesC, 20 degreesC and 40 degreesC. Additionally, fresh plasma samples containing either benzoylecgonine (BZE), ecgonine methyl ester (EME) or ecgonine (ECG) were stored at 4 degreesC and 20 degreesC. Data were established using subsequent solid-phase extraction procedures and high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry for isolation and quantitation of COC, BZE, EME, and ECG. COC, BZE, and EME concentrations decreased with increasing storage temperature and time after an apparent first-order reaction kinetic. Only ECG appeared to be stable at storage temperatures as high as 20 degreesC for the entire observation period. At 40 degreesC, the amount of ECG produced from hydrolysis of COC still totalled 80% of the initial COC concentration. Hydrolysis of COC to EME occurred more rapidly in plasma than in blood. The dynamic degradation profiles obtained were dependent on the storage temperature. The conversion of COC to BZE, EME, and ECG appeared to be stoichiometric at all time intervals at storage temperatures of 4 degreesC and 20 degreesC. The presence of any hydrolysis product of COC in blood or plasma constitutes confirmatory evidence of COC incorporation, and determination of ECG seems most promising even in samples stored under unfavorable conditions.

Chromatography, High Pressure Liquid↗
PubMed2000

Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans.

Extracellular heme derived from hemoglobin following hemorrhage or released from dying cells induces the expression of heme oxygenase-1 (HO-1, HSP-32) which metabolizes heme to the gaseous mediator carbon monoxide (CO), iron (Fe) and biliverdin. Biliverdin and its product bilirubin are powerful antioxidants. Thus, expression of HO-1 is considered to be a protective mechanism against oxidative stress and has been described in microglia, astrocytes and neurons following distinct experimental models of pathological alterations to the brain such as subarachnoidal hemorrhage, ischemia and traumatic brain injury (TBI) and in human neurodegenerative diseases. We have now analyzed the expression of HO-1 in human brains following TBI (n = 28; survival times: few minutes up to 6 months) and focal cerebral infarctions (FCI; n = 17; survival time: < 1 day up to months) by immunohistochemistry. Follwing TBI, accumulation of HO-1+ microglia/macrophages at the hemorrhagic lesion was detected as early as 6 h post trauma and was still pronounced after 6 months. In contrast, after FCI HO-1+ microglia/macrophages accumulated within focal hemorrhages only and were absent in non-hemorrhagic regions. Further, HO-1 was weakly expressed in astrocytes in the perifocal penumbra. In contrast to experimental data derived from rat focal ischemia, these results indicate a prolonged HO-1 expression in humans after brain injury.

Adolescent↗
PubMed2000

Teaching model for intraoperative spinal sonography in spinal fractures. An experimental study.

To improve the technique of intraoperative sonography of the spinal canal, a teaching model of the thoracolumbar spine was developed. It allows to simulate the typical spinal stenosis of a vertebral fracture and the sonographic procedure to detect and measure such a lesion. Moreover, partial laminectomy and modification of a fixateur interne set-up, which are preconditions for successful sonography, can be simulated. Independent of the surgical qualification, a high precision in sonographic localisation and measurement of the spinal canal stenosis was achieved by the training. The results could be validated in the cadaveric model. Thus, sonographic expertise acquired with the teaching model proved to be reliable in the clinical situation.

Cadaver↗
PubMed2000

Detection of gunshot residues in routine CTs.

The forensic assessment of non-fatal gunshot wounds often proves to be difficult as wounds have usually been cleaned and protected with a sterile bandage by the time of the examination. The aim of our investigation was to test the possible application of computed tomography (CT) for the forensic assessment. Doing so raised the questions whether gunshot residues in the soft tissues, detected by means of 3-dimensional CT, can be used as evidence of a close-range shot and whether conclusions can be drawn pertaining to the range of the shot or the type of bullet used based on the distribution of the radiologically detectable material? In this experimental study 39 shots were fired at fresh pig skin and it was possible to distinguish shots fired from distances of more than 10 cm and contact shots independent of the type of bullet. For unjacketed lead bullets, radiopaque material could be seen in the depth of the entrance would for firing distances up to 10 cm. In individual cases, CT data and the 3-D reconstruction could provide valuable information in the forensic assessment of patients with gunshot wounds.

Animals↗
PubMed2000

Lesion-associated accumulation of uPAR/CD87- expressing infiltrating granulocytes, activated microglial cells/macrophages and upregulation by endothelial cells following TBI and FCI in humans.

Urokinase-type plasminogen activator receptor (uPAR/CD87) together with its ligand, urokinase-type plasminogen activator (uPA), constitutes a proteolytic system associated with tissue remodelling and leucocyte infiltration. uPAR is a member of the glycosyl phosphatidyl inositol (GPI) anchored protein family. The functional role of uPAR comprises fibrinolysis by conversion of plasminogen to plasmin. In addition, uPAR promotes cell adhesion, migration, proliferation, re-organization of the actin cytoskeleton, and angiogenesis. Furthermore, uPAR is involved in prevention of scar formation and is chemoattractant to macrophages and leucocytes. In order to investigate the pathophysiological role of uPAR following human CNS injury we examined necrotic brain lesions resulting from traumatic brain injury (TBI; n = 28) and focal cerebral infarctions (FCI; n = 17) by immunohistochemistry. Numbers of uPAR+ cells and uPAR+ blood vessels were counted. Following brain damage, uPAR+ cells increased significantly within 12 h, reached a maximum after 3-4 days and remained elevated until later stages. uPAR was expressed by infiltrating granulocytes, activated microglia/macrophages and endothelial cells. Numbers of uPAR+ vessels increased in parallel subsiding earlier following FCI than post TBI. The restricted, lesion-associated accumulation of uPAR+ cells in the brain parenchyma and upregulated expression by endothelial cells suggests a crucial role for the influx of inflammatory cells and blood-brain barrier (BBB) disturbance. Through a failure in BBB function, uPAR participates in formation of brain oedema and thus contributes to secondary brain damage. In conclusion, the study defines the localization, kinetic course and cellular source of uPAR as a potential pharmacological target following human TBI and FCI.

Adolescent↗
PubMed1999

The detection of dihydrocodeine and its main metabolites in cases of fatal overdose.

The levels of dihydrocodeine found in impaired individuals and in fatalities show a wide overlap in the ranges. Among other factors, the genetically controlled metabolism of dihydrocodeine should play an important role in dihydrocodeine toxicity. For the first time, the most important metabolites of dihydrocodeine were investigated in femoral blood from three fatal cases by simultaneous determination using HPLC and native fluorescence for detection. The amount of parent drug always exceeded dihydrocodeine-glucuronide formation and dihydromorphine concentrations ranged from 0.16-0.21 mg/L. The similar binding affinities of dihydromorphine and morphine to mu-opioid receptors suggest similar pharmacological effects and adverse reactions. The determination of the pharmacologically active metabolites should help to clarify the cause of death in fatal cases especially if a relatively low concentration of the parent drug is found.

Adult↗
PubMed1998

Postmortem distribution of dihydrocodeine and metabolites in a fatal case of dihydrocodeine intoxication.

A report of a fatal dihydrocodeine ingestion under substitution therapy is given. Quantitation of dihydrocodeine, dihydromorphine, N-nordihydrocodeine, dihydrocodeine-6-, dihydromorphine-6- and dihydromorphine-3-glucuronide was performed simultaneously after solid-phase extraction prior to HPLC analysis, and the analytes were detected using their native fluorescence. Postmortem concentrations of blood samples from different sampling sites as well as from liver, kidney and cerebrum are reported. A hair sample was investigated to prove long-term use of the substitute drug. Site-to-site differences of the analytes from blood samples were very small. The partition behavior of the opioid glucuronides depended on the hematocrit value of the particular blood sample. Most important findings seemed that dihydromorphine and dihydromorphine-6-glucuronide concentrations decisively contributed to the toxicity of dihydrocodeine. This case report outlines that in dihydrocodeine related deaths the concentrations of the pharmacologically active metabolites should additionally be determined for reliable interpretation.

Adult↗
PubMed1998

A preliminary study on the stability of benzodiazepines in blood and plasma stored at 4 degrees C.

An approach to determine the stability of benzodiazepines and some of their metabolites (n = 13) by means of a routinely applied gas chromatographic method using electron capture detection was made in this preliminary study. Validation data of the method are given. Spiked blood and plasma samples were stored at 4 degrees C and analysed at selected times up to 240 days. The concentrations of all analytes had decreased to at least 60% of the original levels at the end of the observation period. A clear pattern of breakdown could not be established. The data obtained suggest that results from long-term stored samples should be interpreted cautiously. Further investigations concerning the stability of drugs in blood and plasma samples, additional methods of identification and determination as well as the establishment of optimal storage conditions seem necessary.

Benzodiazepines↗
PubMed1998

Hemoglobin diffusion across a venous wall: an experimental study.

The aim of this study was to investigate the permeation behavior of a large molecule through a venous wall; hemoglobin was chosen as a model substance. In vitro experiments were performed using a Chien-Valia diffusion chamber. Postmortem, hemolyzed, and fresh nonhemolyzed blood samples were investigated as permeants. Vein patches from vena cava inferior and vena jugularis interna were used as diffusion barriers. Applying this technique, extravasation of hemoglobin was detectable. The portion of hemoglobin molecules passing through the vascular wall depended on time, vein type, and graduation of hemolysis. The passage of hemoglobin across the wall of a large vein suggests intravascular changes in drug concentrations from postmortem blood samples not to be restricted on the unbound portion of the particular drug.

Diffusion↗
PubMed1997

Insulin injection sites: morphology and immunohistochemistry.

In a case of insulin suicide in a nondiabetic woman, insulin was detected in routinely formalin fixed and paraffin embedded subcutaneous injection marks, in spite of a post-morterm interval of 24 days. Around birefringent crystalline material, probably zinc phosphate, immunohistochemistry revealed granular insulin depots as well as an insulin staining along the lipocyte membranes. A cellular reaction of granulocytic character was present, with an uptake of insulin by inflammatory cells.

Autopsy↗
PubMed1997

[Biomechanics of combined Kirschner wire osteosynthesis in the human model of unstable dorsal, distal radius fractures (Colles type)].

In an experimental study, the biomechanical qualities of the combined Kirschner wire osteosynthesis (KWO) in the unstable Colles' fracture were analyzed. This type of pin fixation is our preferred osteosynthesis in the treatment of unstable Colles' fracture because it allows immediate functional therapy. It represents a modification of Kapandji's dynamic KWO, compensating for the insufficient volar stability by means of the conventional static KWO. Clinical experience according to the anatomical and functional results, was very encouraging suggesting that a clinical concept based on the biomechanical principles of combined KWO and its single components should be constituted. Simulation of the unstable Colles' fracture was realized by dorsal wedge osteotomy of the distal end of the radius using cadaveric material. This fracture model was subsequently pinned using the different KWO types and tested by a standardized vector energy testing device regarding its stability in the four main loading directions. The combined KWO unifies the advantage of volar stability of the conventional KWO with the high dorsal stability of dynamic KWO. The main functional principle of dynamic KWO with regard to its axial stability consists in the repositioning of the dorsal bone fragmentation zone and hence the reconstitution of cortical load transmission. Besides its good stabilization, dynamic KWO also leads to optimal alignment of the distal metaphyseal fragment. Furthermore, the experiments yielded important information about technical aspects of the surgical procedure, which helps us to avoid anatomical and functional deficiencies. Based on these experimental findings, the surgical technique of combined KWO was standardized.

Biomechanical Phenomena↗
PubMed1997

[The prospects for Kirschner-wire osteosynthesis in the dorsally unstable distal radius fracture (Colles' type)].

The following experimental study was conducted to develop biocompatible methods of osteosynthesis in fractures of the distal radius and to evaluate their stability. A model of dorsal wedge osteotomy in the distal radial metaphysis was used to develop the surgical technique and to test the stability of the alternative methods of osteosynthesis. The concept for this model was based on commercially available materials which were either biodegradable or osteoconductive. Four different forms of biocompatible osteosynthesis were compared to combined Kirschner wire osteosynthesis (KWO), our preferred method of treatment of unstable Colles fracture. Biocompatible osteosynthesis was achieved with an invasivity and stability comparable to that of KWO. In conclusion, injection osteosynthesis exceeded the other biocompatible methods of osteosynthesis in all respects. Regarding the recent developments in injectable materials for osteosynthesis it offers the best perspective for clinical application.

Biocompatible Materials↗
PubMed1997

An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall.

A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.

Biological Transport↗
PubMed1996

Estimation of sex on the basis of radiographs of the calcaneus.

Lateral and anteroposterior radiographs of the ankles of 800 Central Europeans aged 20 to 79 were analyzed with regard to sexual dimorphism. All the distances, but not the angles, of the calcaneus were much larger in males than in females. Approximately 80% of the study sample could be sexed correctly by classifying all specimens greater than 86.0 mm in length as male and those less than 86.0 mm as female. The prevalence of os tibiale externum was 8.0 and 2.6% and the prevalence of plantar heel spur was 16.3 and 6.5% (increasing with age) for males and females, respectively, being significantly more frequent in females. On the other hand, the bone island frequencies were 9.1% in males and 4.8% in females. Our study suggests that radiographs of the ankle are a convenient, rapid, cheap and non-invasive means for estimating sex.

Adult↗
PubMed1996

Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose.

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of the inferior vena cava, the superior vena cava, the femoral and subclavian veins, and the right and left ventricles were examined for morphine, morphine-3-glucuronide and morphine-6-glucuronide, hematocrit and water content. Drug concentrations were determined by HPLC based on the native fluorescence of the analytes. Morphine glucuronides proved to be stable for a time period of 72 h. The water content ranged from 65 to 83% and hematocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences observed for drug concentrations from different sampling sites. The differences could neither be attributed to incomplete distribution during life-time nor to a diffusion process following the different distribution volumes of morphine and its conjugates. A definite relationship between the ratio of the molar concentrations of morphine and its glucuronides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and changes over time and tissue concentrations should be analysed.

Adult↗