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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed2002

Appropriate neurological evaluation and multimodality magnetic resonance imaging in eclampsia.

HYPOTHESIS: Simultanagnosia is common in eclampsia and a visuospatial test may be the most appropriate method in assessing the degree and monitoring of neurological deficit. AIM: To determine a sensitive clinical test for the degree of neurological deficit in eclampsia and in monitoring neurological change. METHODS: Thirty women with eclampsia were evaluated by clinical neurological quantitative scales including the Canadian Neurological Scale, Glasgow Coma Scale, Mini-Mental State Examination, a validated Cookie Theft Picture Test (CTPT), magnetic resonance imaging (MRI) (T1/T2), diffusion weighted imaging (DWI) and magnetic resonance angiography (MRA). RESULTS: The CTPT, used to measure simultanagnosia, had a sensitivity of 100% (95% CI: 84.5-100), specificity of 33.3% (95% CI: 1.8-87.5) with positive predictive value of 93.1% (95% CI: 75.8-98.8) and negative predictive value of 100% (95% CI: 5.5-100). The degree of agreement between simultanagnosia as measured by CTPT and DWI was 93.3% (Kappa=0.474; P=0.001). Standard MRI compared with DWI had a sensitivity of 77.8% (95% CI: 57.3-90.6), specificity of 100% (95% CI: 31-100), positive predictive value of 100% (95% CI: 80.8-100) and negative predictive value of 33.3% (95% CI: 9-69.1). The degree of agreement between standard MRI and DWI was 90%, this was statistically significant (Kappa=0.412: P=0.001). CONCLUSIONS: The validated CTPT for simultanagnosia was abnormal in the majority (n=29; 96.7%) of eclamptic patients with other neurological scales normal. Standard MRI and DWI showed excellent correlation with this simple bedside clinimetric evaluation. The oedema in eclampsia is primarily of vasogenic origin.

Adolescent↗
PubMed2002

Instrumental evaluation of retinoid-induced skin irritation.

BACKGROUND/PURPOSE: Retinoids like tazarotene are approved for the treatment of chronic plaque psoriasis. In the beginning of topical retinoid therapy, 15-20% of the patients suffer from mild to moderate adverse reactions with burning and erythema. The aim of the study was to find predicative parameters of the individual irritative potential and to suggest options to reduce these initial irritations. METHODS: Twenty in-patients with different skin types (1 + 2: 11, 3 + 4: 9), with chronic plaque psoriasis were included in this open study. In each patient, 7 randomized plaques on the forearm were treated for 14 days on different ways: test area 1: morning (m) and evening (e) placebo, test area 2: placebo (m) and tazarotene 0.05% (e), test area 3: placebo (m) and tazarotene 0.1% (e), test area 4: calcipotriol (m) and calcípotriol (e), test area 5: mometasone furoate (m) and tazarotene 0.05% (e), test area 6: mometasone furoate (m) and tazarotene 0,1% (e), test area 7: placebo (m) and tazarotene in increasing concentrations (e), test area 8: healthy skin for control. Before and after therapy, skin barrier function, blood flow and plaque thickness in 20-MHz sonography were assessed in different test areas intraindividually by non- invasive biophysical measurements. RESULTS: After 14 days of therapy, tazarotene 0.05% and 0.1% produced a stronger increase of laser Doppler flow in patients with skin type 1 and 2 than in patients with skin type 3 and 4. When using the combination therapy of tazarotene and mometasone, the laser Doppler flow was significantly lower than in tazarotene as monotherapy. 20-MHz-ultrasound showed a significant decrease in the thickness of the echo-poor band in all topical therapy regimens compared to placebo. Patients of skin type 1 and 2 reached a higher density of the dermis than patients of skin type 3 and 4, meaning a stronger decrease of inflammatory infiltration and acanthosis. CONCLUSION: Adapting retinoid therapy to the patient's skin type can reduce the initial irritative side-effects. During the first days, patients with skin type 1 or 2 should add a medium potency corticosteroid. Stronger skin irritation caused by tazarotene therapy increases therapy effects.

Administration, Cutaneous↗
PubMed2002

Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.

In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.

Adult↗
PubMed2002

Applications of autofluorescence for characterisation of biological systems (biomonitoring).

We describe a system capable of measuring the laser induced fluorescence emission of two coenzymes (NADH and FAD) via an optical fibre for in vivo monitoring of anatomical, physiological or pathological changes in biological systems. This optical technique permits the measurement of changes in the metabolism of cells in real-time and is nearly non-destructive. We present results of examinations on the localisation of transitions between different tissue and the monitoring of the oxygenation level (ischemia) in muscle or changes in the cellular activity of bacteria in a bioreactor.

Animals↗
PubMed2002

[Endoscopic 3-D imaging--measuring biological surfaces].

The precise endoscopical measurement of topometrical structures of organs will overcome limitations in present minimal invasive surgery and lead to new operation techniques. This paper describes a research project concerning an endoscopical 3D-measurement system based on optical techniques. We will introduce prototype endoscopes for minimal invasive 3D-measurements and the applied photogrammetrical algorithms for acquiring the topometrical structures. The influence of major organ surface properties on the measurement will be discussed and first results will be presented.

Endoscopes↗
PubMed2002

Screening of stabilized crosslinked polyethylene using a novel wear tester.

A novel pin-on-disk type wear tester is described allowing a rapid screening of different types of polyethylene under both unidirectional and multidirectional sliding motion. The wear of four polyethylene materials sliding against a roughened CoCrMo alloy was evaluated: a non-irradiated UHMWPE, a UHMWPE irradiated with a dose of 25 kGy in air, and two types of crosslinked UHMWPE (100 kGy, air), which were subjected to a stabilization heat treatment in nitrogen at 155 degrees C for 72 hours (XLPE I) and in water at 130 degrees C for 72 hours (XLPE II), respectively.Under multidirectional sliding conditions both types of XLPE exhibited significantly less wear with respect to the 25 kGy irradiated UHMWPE and the non-irradiated UHMWPE, even under the rough counterface conditions applied. Under unidirectional sliding motion both types of XLPE exhibited the highest wear of all materials tested, because the orientation hardening effect acting under linear lubricated condition is less pronounced for crosslinked polyethylene.

Dose-Response Relationship, Radiation↗
PubMed2001

[Hospitalizations in a cohort of 175 severely drug-addicted patients of a medically managed opiate withdrawal project].

In this study we investigated a population of 175 seriously drug addicted patients. They were randomised in a controlled opiate maintenance program in Basel, Switzerland. We investigated hospitalizations in the time period three years before entry into the program and approximately 3.5 years after entry into this program. The mean age was 28.4 years, the mean drug injection time was 8.8 years. 82.6% of the patients were seropositive for HCV and 21.5% were HIV-infected. We observed 223 hospitalizations in 100/175 patients during the observation period of 6.5 years. Most commonly infections (n = 94), different diseases of internal medicine (n = 44) and surgical diseases (n = 41) led to hospitalization. Altogether, we found no decrease of the incidence of hospitalisations. However, there was a significant decrease of directly drug-induced diseases (p < 0.05). So far, hospitalizations did not diminish in this well-controlled opiate maintenance program. However, as shown in earlier studies, the incidence of HIV drastically dropped. Hence, it may be that a longer follow-up may prove beneficial regarding the incidence of hospitalisations.

Adult↗
PubMed2001

Recombinant Semliki Forest virus for over-expression and pharmacological characterisation of the histamine H(2) receptor in mammalian cells.

We describe the use of recombinant Semliki Forest virus (SFV) vectors for efficient expression of the rat histamine H(2) (rH(2)) receptor in COS-7 (African green monkey kidney cells) cells. Recombinant SFV-infected COS-7 cells express the histamine rH(2) receptor in a time-dependent fashion with a maximum expression level of 50 pmol mg(-1) after 40 h. SFV-mediated histamine rH(2) receptor expression shows similar pharmacological properties as the receptor expressed transiently or stably in mammalian cells. In addition, we demonstrate the pharmacological and functional characterisation of the D(115)N mutated histamine rH(2) receptor. It has been shown that the D(115)N mutation renders the receptor constitutively active and structurally unstable. The rapid onset of and high maximal expression levels obtained from SFV-infected COS-7 cells enabled us to characterise this mutant receptor. We prove that recombinant SFV vectors are powerful tools for heterologous expression of G-protein-coupled receptors and that one can achieve both the high-level gene expression described for baculovirus-infected insect cells and the use of mammalian cells as hosts.

Animals↗
PubMed2001

Mechanism of activation of an immunosuppressive drug: azathioprine. Quantum chemical study on the reaction of azathioprine with cysteine.

Azathioprine is an important drug used in the therapy of autoimmune disorders and in preventing graft rejection. Its molecule is composed of two main moieties: mercaptopurine and imidazole derivative. It is an immunosuppressive agent whose biological activity results from its in vivo mercaptolysis mediated by a nucleophilic attack on the C(5i) atom of imidazole ring of the azathioprine molecule. Solvation model SM5.4 with the PM3 Hamiltonian have been applied to model the reaction of azathioprine with cysteine. The employed quantum mechanical method shed new light on the mechanism of the reaction of azathioprine with cysteine in aqueous solution. The obtained results indicated that the first step in the reaction most likely involves the nucleophilic attack of the COO(-) of cysteine on the C(5i) atom of the imidazole ring of azathioprine, followed by a subsequent intramolecular attack of the SH group of the cysteine residue. It was shown that biogenic thiols such as glutathione or cysteine facilitate the first and crucial step of azathioprine metabolism, due to the presence of COO(-), SH, and NH(3)(+) groups in their molecules.

Azathioprine↗
PubMed2001

Development of a pharmacophore model for histamine H3 receptor antagonists, using the newly developed molecular modeling program SLATE.

New molecular modeling tools were developed to construct a qualitative pharmacophore model for histamine H3 receptor antagonists. The program SLATE superposes ligands assuming optimum hydrogen bond geometry. One or two ligands are allowed to flex in the procedure, thereby enabling the determination of the bioactive conformation of flexible H3 antagonists. In the derived model, four hydrogen-bonding site points and two hydrophobic pockets available for binding antagonists are revealed. The model results in a better understanding of the structure-activity relationships of H3 antagonists. To validate the model, a series of new antagonists was synthesized. The compounds were designed to interact with all four hydrogen-bonding site points and the two hydrophobic pockets simultaneously. These ligands have high H3 receptor affinity, thereby illustrating how the model can be used in the design of new classes of H3 antagonists.

Animals↗
PubMed2001

Coherent external and internal phonons in quasi-one-dimensional organic molecular crystals.

We have directly time resolved coherent phonon oscillations in quasi-one-dimensional organic crystals of MePTCDI ( N-N'-dimethylperylene-3,4,9,10-dicarboximide), using femtosecond pump-probe experiments. We observe both higher-energy oscillations caused by intramolecular vibrations (internal phonons) and, for the first time in a quasi-one-dimensional organic system, lower-energy modulations which are related to coherent lattice phonons (external phonons). For internal A(g) vibrations, the coherence decay time of about 2 ps is almost independent of the mode. In contrast, the damping time of the external phonons increases strongly with decreasing energy.

Journal Article↗
PubMed2001

[Complications after high dose therapy and autologous stem cell transplantation. Retrospective study of an unselected patient sample].

BACKGROUND: High-dose therapy (HDT) with autologous blood stem cell transplantation (ASCT) has become the therapy of choice for patients with specific hematologic neoplasms. Although pancytopenia after HDT with stem cell support is of relatively short duration, complications may be severe and life-threatening. In unselected patients with hematologic and solid tumor malignancies, only few data have been published regarding complications. We therefore analyzed the rate of infection and toxicity in patients with different neoplasms undergoing HDT and ASCT. PATIENTS AND METHODS: From 6/96 to 12/99 42 patients received 54 HDT and ASCT (nine tandem transplants and one triple transplant). The median age was 55 years (range 25-74 years) with equal sex distribution. 30 patients suffered from hematologic malignancies and twelve from solid tumors. RESULTS: Infections were the major cause for complications followed by mucositis, pain and diarrhea. In four patients a positive cytomegalovirus polymerase chain reaction (CMV-PCR) was detected. In two patients this positive test result was accompanied by clinical symptoms of CMV infection. One patient developed lung fibrosis due to busulfan (WHO 4 degrees) and additionally a veno-occlusive disease (VOD) of the liver (WHO 4 degrees). Two patients (4%) died due to CMV pneumonia and multiple organ failure after idiopathic pneumonia, respectively. Four patients developed secondary neoplasms (two patients myelodysplastic syndromes, two patients solid tumors). Three of them had been heavily pretreated. We further analyzed whether the following parameters had an influence on the rate of complications: tumor diagnosis (hematologic vs. solid), number of pretreatment protocols (< 2 vs. > or = 2), CD34+ cell count (< median CD34+ cell count vs. > or = median CD34+ cell count), age (< or = 55 years vs. > 55 years), mucositis (WHO 1-2 degrees vs. 3-4 degrees) and conditioning regimen (myeloablative vs. myelosuppressive). The infection rate was higher in patients receiving myeloablative therapy compared to patients with myelosuppressive conditioning and the platelet count recovery was slower. In patients receiving a higher CD34+ cell count, time until platelets reached > 50/nl was shorter than in patients with a lower CD34+ cell count. Patients with > or = 2 pretreatment protocols had a higher infection rate than patients with < 2 pretreatments. Patients suffering from severe mucositis (WHO 3-4 degrees) exhibited a slower platelet recovery and a higher infection rate. No difference was noted in the complication rate for the other parameters (tumor diagnosis, age). CONCLUSION: Complication rate and mortality in this heterogeneous patient group were not different from the data of other authors describing selected patients receiving a uniform conditioning regimen or having a distinct disease. The complication rate is influenced by the number of pretreatment protocols, conditioning regimens and the number of transplanted CD34+ cells.

Adult↗
PubMed2001

Effects of substituting a OH group by a F atom in D-glucose. Ab initio and DFT analysis.

High-level ab initio and DFT methods up to MP2/6-311++G//B3LYP/6-31G and B3LYP/6-311++G//B3LYP/6-31G levels have been used to assess the relative energies of 17 different structures of D-glucose and 13 different structures of 4-deoxy-4-fluoro-D-glucose. The structures were confirmed to correspond to minima on the potential energy surface at the RHF/6-31G level. Solvation Model 5.4/AM1 was used to calculate the effects of aqueous solution. The substitution of a OH group by a F atom does not much change the shape and electrostatic potential around corresponding conformers, but in the gas phase it destabilizes the cooperative network of intramolecular hydrogen bonds. This destabilization mostly affects structures with a chain of intramolecular hydrogen bonds oriented counterclockwise, as fluorine is unable to donate a hydrogen bond and therefore causes a gap in the chain. In contrast, for clockwise-oriented networks of hydrogen bonds, the fluorine can act as an acceptor at the end of a chain of cooperative hydrogen bonds. A slightly higher energy of anomeric and exo-anomeric stabilization is another effect of substituting the fourth hydroxyl group by a fluorine atom in D-glucose, observed both in the gas phase and in aqueous solution. For this reason, the alpha anomers contribute more to the equilibrium population of structures of 4-deoxy-4-fluoro-D-glucose than D-glucose. In aqueous solution, both D-glucose and its 4-deoxy-4-fluoro analogue are present as a mixture of mainly three corresponding structures. This indicates that 4-deoxy-4-fluoro-D-glucose is a good substitute for D-glucose in terms of its biochemical and biological activity. Moreover, this suggests that, for molecules with limited conformational freedom, the substitution of a OH group by a F atom is very likely to lead to a potential new drug. In contrast, it had already been shown that, for conformationally labile aliphatic compounds, replacement of a hydroxyl by a fluorine increases conformational diversity, so the fluorine-containing aliphatic molecules were not likely to be an example of a successful drug design. On the other hand, this work shows that, among molecules with limited conformational freedom, such as cyclic compounds, one is very likely to find targets for a successful rational drug design.

Fluorine↗
PubMed2001

Transcriptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells.

PURPOSE: The aim of the experiments was to analyze the mRNA expression pattern and verify the repression of FN gene expression in laryngeal squamous cell carcinoma (SCC) cells in comparison with benign mucosal keratinocytes. METHODS: Messenger RNA from SCC cells and benign keratinocytes was reverse transcribed and subjected to PCR following differential display (DD) analysis of the amplicons. Northern hybridization was carried out to confirm the reduction of the FN-mRNA expression in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. Quantitation of protein synthesis was performed with homogenates of fresh tumor biopsies and their normal phenotypes, as well as of benign keratinocytes and laryngeal SCC cell lines, respectively, using ELISA. In the liposome-mediated transient transfection assay, FN promoter activity was analyzed by linking the FN promoter sequence to the chloramphenicol acetyltransferase (CAT) reporter gene. Transfection efficacy was monitored by co-transfection with pGL3 control vector. RESULTS: A 191 bp mRNA fragment revealing a 99% homology with the human FN-mRNA was detected, the expression of which was repressed 20 times as much in SCC cells as compared to benign phenotypes. Northern hybridization confirmed the distinctly reduced expression of FN-mRNA in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. The quantitation experiments showed a correlation between the range of FN synthesis and the expression of FN-mRNA in cell lines and the biopsies which were used. The 1.28 kb FN gene promoter drove expression of the CAT reporter gene, which was similar to the FN-mRNA expression showed by DD and Northern hybridization. CONCLUSIONS: The mechanisms leading to the low level of FN in many tumors have not yet been sufficiently investigated. Our findings suggest that the decrease of FN in laryngeal SCC cells is transcriptionally regulated.

Base Sequence↗
PubMed2001

Control of the efficiency of agonist-induced information transfer and stability of the ternary complex containing the delta opioid receptor and the alpha subunit of G(i1) by mutation of a receptor/G protein contact interface.

Fusion proteins were constructed between the delta opioid receptor and forms of the alpha subunit of G(i1) in which cysteine(351) was mutated to a range of amino acids. GDP reduced the binding of the agonist [(3)H]DADLE but not the antagonist [(3)H]naltrindole to both the receptor alone and all the delta opioid receptor-Cys(351)XaaG(i1)alpha fusion proteins. For the fusion proteins the pEC(50) for GDP was strongly correlated with the n-octanol/H(2)O partition co-efficient of G protein residue(351). Fusion proteins in which this residue was either isoleucine or glycine had similar observed binding kinetics for [(3)H]DADLE. However, the rate of dissociation of [(3)H]DADLE was substantially greater for the glycine-containing fusion protein than that containing isoleucine, indicating that more hydrophobic residues imbued greater stability to the agonist-receptor-G protein ternary complex. This resulted in a higher affinity of binding of [(3)H]DADLE to the fusion protein containing isoleucine(351). In expectation with the binding data, maximal DADLE-stimulated GTP hydrolysis by the isoleucine(351)-containing fusion protein was two-fold greater and the potency of DADLE seven-fold higher than for the version containing glycine. These results demonstrate that the stability of the ternary complex between delta opioid receptor, G(i1)alpha and an agonist (but not antagonist) ligand is dependent upon the nature of residue(351) of the G protein and that this determines the effectiveness of information flow from the receptor to the G protein.

Cell Membrane↗
PubMed2001

The RNA world of plant mitochondria.

Mitochondria are well known as the cellular power factory. Much less is known about these organelles as a genetic system. This is particularly true for mitochondria of plants, which subsist with respect to attention by the scientific community in the shadow of the chloroplasts. Nevertheless the mitochondrial genetic system is essential for the function of mitochondria and thus for the survival of the plant. In plant mitochondria the pathway from the genetic information encoded in the DNA to the functional protein leads through a very diverse RNA world. How the RNA is generated and what kinds of regulation and control mechanisms are operative in transcription are current topics in research. Furthermore, the modes of posttranscriptional alterations and their consequences for RNA stability and thus for gene expression in plant mitochondria are currently objects of intensive investigations. In this article current results obtained in the examination of plant mitochondrial transcription, RNA processing, and RNA stability are illustrated. Recent developments in the characterization of promoter structure and the respective transcription apparatus as well as new aspects of RNA processing steps including mRNA 3' processing and stability, mRNA polyadenylation, RNA editing, and tRNA maturation are presented. We also consider new suggestions concerning the endosymbiont hypothesis and evolution of mitochondria. These novel considerations may yield important clues for the further analysis of the plant mitochondrial genetic system. Conversely, an increasing knowledge about the mechanisms and components of the organellar genetic system might reveal new aspects of the evolutionary history of mitochondria.

Base Sequence↗
PubMed2001

Optimized mapping of slow pathway ablation guided by subthreshold stimulation: a randomized prospective study in patients with recurrent atrioventricular nodal re-entrant tachycardia.

OBJECTIVES: This randomized prospective study sought to assess the value of slow pathway (SP) mapping and ablation guided by subthreshold stimulation (STS) in comparison with a strategy based on conventional criteria. BACKGROUND: Previous studies have demonstrated that STS can be used as a highly specific and sensitive marker for successful SP ablation in the setting of atrioventricular nodal re-entrant tachycardia (AVNRT). Nonetheless, thus far this mapping strategy has not been investigated in contrast with the conventional approach. METHODS: One hundred patients with sustained AVNRT were included. Fifty patients (group A) were randomly assigned to endocardial mapping and SP ablation using currently established criteria. In the other 50 patients (group B), SP ablation was guided by STS mapping. In group B patients, only radiofrequency current (RFC) was applied if additionally constant current STS (up to 5 mA) during AVNRT interrupted the tachycardia due to selective block within the SP. RESULTS: Termination of AVNRT without apparent capture was observed during STS in 47 of 50 group B patients (94%). In all cases, this effect was indicative for successful subsequent SP ablation. The mean number of RFC pulses required for successful SP ablation was significantly lower in patients assigned to the STS-guided strategy (1.6 +/- 1.3 vs. 3.9 +/- 3.4; p = 0.0003). Similarly, the mean procedure duration was shorter in the STS group (156.9 +/- 33.5 vs. 173.2 +/- 49.7 min; p = 0.0221); the fluoroscopy time was comparable between both groups (14.1 +/- 8.7 vs. 16.9 +/- 10.6 min; p = 0.1278). CONCLUSIONS: Subthreshold stimulation is an effective method for detection of target sites for selective SP ablation. This technique helps to minimize the number of RFC pulses without prolongation of the overall procedure and fluoroscopy time required for SP ablation.

Aged↗