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Biomedical subjects

G Müller

Publications and source records attributed to G Müller.

At least 73 records · Page 4Linked to original sources
PubMed2001

Discovery and evaluation of piperidinyl carboxylic acid derivatives as potent alpha(4)beta(1) integrin antagonists.

Piperidinyl carboxylic acid-based derivatives were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the alpha(4)beta(1) integrin (VLA-4, very late antigen 4) and the vascular cell adhesion molecule 1 (VCAM-1). Compounds 2a-h inhibited the adhesion in a cell-based assay in the low and sub micromolar range, a pharmacokinetic study of 2d is reported.

Area Under Curve↗
PubMed2001

Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastasis.

PURPOSE: The aim of this study was to determine the energy (J/mm3 tumor volume) and temperature required for a complete laser-induced thermotherapy (LITT) of experimental liver tumors, and to find out causes and areas of local recurrence followed by incomplete treatment. METHODS: In VX-2 tumor-bearing rabbits LITT was performed using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) with a diffuser-tip applicator and a temperature feedback system. The animals were randomized into four groups (n = 20) that differed in the target temperature at the tumor border as follows: 45 degrees C, 50 degrees C, 55 degrees C and 60 degrees C. The target temperature was held for 10 min constant. Histologic examination (hematoxylin and eosin [H and E], nicotinamide adenine dinucleotide phosphate [NADPH]-dehydrogenase) was performed at 0 h, 24 h, 96 h, and 14 days after LITT. RESULTS: The pretreatment tumor volume of 2191 +/- 61 mm3 was the same for all groups (p > 0.05). Energy up to target temperature and total energy required, lesion size, and the rate of incomplete tumor ablation (recurrences) are listed below (ap < 0.05, Kruskal-Wallis test). Histologically, two forms of local recurrences could be differentiated intralesionary and extralesionary. CONCLUSIONS: To achieve complete in situ ablation under the given conditions, it is necessary to apply laser energy of 3 J/mm3 tumor volume. A minimum temperature of 60 degrees C on the tumor border presumed an application of 10 min. Recurrence was found outside the coagulation zone (extralesionary) and in high vascularized areas within the coagulation zone (intralesionary).

Animals↗
PubMed2001

Carbon nanotube bags: catalytic formation, physical properties, two-dimensional alignment and geometric structuring of densely filled carbon tubes.

The catalytic CVD synthesis, using propyne as carbon precursor and Fe(NO3)3 as catalyst precursor inside porous alumina, gives carbon nanotube (CNT) bags in a well-arranged two-dimensional order. The tubes have the morphology of bags or fibers, since they are completely filled with smaller helicoidal CNTs. This morphology has so far not been reported for CNTs. Owing to the dense filling of the outer mother CNTs with small helicoidal CNTs, the resulting CNT fibers appear to be stiff and show no sign of inflation, as sometimes observed with hollow CNTs. The fiber morphology was observed by raster electron microscopy (REM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The carbon material is graphitic as deduced from spectroscopic studies (X-ray diffraction, Raman and electron energy-loss spectroscopy (EELS)). From Mössbauer studies, the presence of two different oxidation states (Fe0 and FeIII) of the catalyst is proven. Geometric structuring of the template by two different methods has been studied. Inkjet catalyst printing shows that the tubes can be arranged in defined areas by a simple and easily applied technique. Laser-structuring creates grooves of nanotube fibers embedded in the alumina host. This allows the formation of defined architectures in the microm range. Results on hydrogen absorption and field emission properties of the CNT fibers are reported.

Journal Article↗
PubMed2001

Evidence of infectious diseases in harbour porpoises (Phocoena phocoena) hunted in the waters of Greenland and by-caught in the German North Sea and Baltic Sea.

The pathological, microbiological and serological findings in harbour porpoises hunted in Greenlandic waters were compared with the findings in animals accidentally caught in fishing gear in the German North Sea and Baltic Sea. The body condition of the Greenlandic animals was good, whereas nine of 23 German harbour porpoises were moderately to markedly emaciated. Both groups were infested with parasites. In the Greenlandic animals parasitism of the aural peribullar cavity with Stenurus minor, of the liver and pancreas with Orthosplanchnus mironovi, of the lungs with Halocercus species and of the subcutaneous and mammary tissue with Crassicauda species was generally associated with a mild inflammatory response. No diseases associated with bacteria were identified in any of the Greenlandic harbour porpoises. In the porpoises from the German North Sea and Baltic Sea, parasites were present in the aural peribullar cavity (S minor), liver (Campula oblonga), first and second gastric compartment (Anisakis simplex) and in the lungs (Pseudalius inflexus and Torynurus convolutus). Moderate to marked pulmonary parasitism and suppurative pneumonia, not observed in the Greenlandic porpoises, were present in 11 and 10, respectively, of the 23 German porpoises. The suppurative pneumonia was attributed to bacterial infection with beta-haemolytic streptococci and Escherichia coil var haemolytica. Four Greenlandic and 10 German porpoises had positive porpoise morbillivirus-specific antibody titres suggesting that the virus was circulating in both populations.

Animals↗
PubMed2001

Integrability and action operators in quantum Hamiltonian systems.

For a (classically) integrable quantum-mechanical system with two degrees of freedom, the functional dependence H=HQ(J1,J2) of the Hamiltonian operator on the action operators is analyzed and compared with the corresponding functional relationship H(p1,q1;p2,q2)=HC(J1,J2) in the classical limit of that system. The former converges toward the latter in some asymptotic regime associated with the classical limit, but the convergence is, in general, nonuniform. The existence of the function H=HQ(J1,J2) in the integrable regime of a parametric quantum system explains empirical results for the dimensionality of manifolds in parameter space on which at least two levels are degenerate. The analysis is carried out for an integrable one-parameter two-spin model. Additional results presented for the (integrable) circular billiard model illuminate the same conclusions from a different angle.

Journal Article↗
PubMed2001

Pharmacokinetics and tissue distribution of the anticholinergics tiotropium and ipratropium in the rat and dog.

Ipratropium, a current treatment for chronic obstructive pulmonary disease (COPD) and tiotropium, a longer acting anticholinergic bronchodilator currently being developed for COPD are structurally related to atropine. In this study, the intravenous (i.v.), oral (p.o.) and intratracheal (i.tr.) single dose pharmacokinetics (PK) of tiotropium and ipratropium were determined in rat and dog. In rats, concentration-time profiles of tiotropium and ipratropium after single i.v. bolus administration of 7-8 mg kg(-1) are similar. Both drugs are highly cleared (Cl between 87 and 150 ml min(-1) kg(-1)) and extensively distributed into tissues (volume of distribution V(ss) between 3 and 15 l kg(-1)). In dogs, this holds also true for both drugs (Cl between 34 and 42 ml min(-1) kg(-1), V(ss) between 2 and 10 l kg(-1)), although different dose regimen were applied (i.v. bolus of 0.08 mg kg(-1) vs. infusion of 0.1 mg kg(-1) h(-1) for 3 h). Tiotropium plasma concentrations increased linearly in rats over a wide dose range following single i.v. administration. Both ipratropium and tiotropium showed a comparable terminal elimination half-life in rat urine (21-24 h) after single i.v. administration, which was much longer than the corresponding half-life in plasma (6-8 h). Whole body autoradiography in rats revealed a broad and rapid tissue distribution of [(14)C]tiotropium radioactivity after single i.v. administration. A comparable distribution pattern has also been reported earlier for ipratropium.

Animals↗
PubMed2001

Continuous changes in the optical properties of liver tissue during laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVE: Laser-induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. To predict the effects of laser applications and to optimize treatment planning in LITT, it is essential to gain knowledge about light distribution in tissue, tissue optical properties (absorption, scattering, anisotropy, penetration depth), and their continuous changes during therapy. STUDY DESIGN/MATERIALS AND METHODS: Measurements of optical properties were performed with a double integrating-sphere system and a laser diode (830 nm). Porcine liver tissue samples were examined in a native state (35 degrees C) and after exposure to different temperatures (45 degrees C to 80 degrees C). RESULTS: Rising temperature was accompanied by a decrease in the absorption coefficient and anisotropy factor and an increase in the scattering coefficient. These changes were only significant in the temperature range of 50 degrees to 65 degrees C (P < 0.01). The optical penetration depth decreased from 3.1mm in the native state to 1.7mm at 65 degrees C (P < 0.01). Above 65 degrees, there was no significant change in the tissue optical properties. CONCLUSIONS: The optical properties of liver tissue change significantly under the influence of tissue heating, resulting in a decreased optical penetration depth. These changes occur mainly in the temperature range of 50 degrees C to 65 degrees C, corresponding to protein denaturation. To ensure a safe and effective procedure, an adjustment of the laser power to the actual penetration depth is recommended during therapy.

Animals↗
PubMed2001

Optical properties of native and coagulated porcine liver tissue between 400 and 2400 nm.

BACKGROUND AND OBJECTIVE: Laser induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. For predicting the effects of laser applications and optimizing irradiation planning in LITT, knowledge about light distribution in tissue, optical tissue properties (absorption, scattering, anisotropy, penetration depth) and their changes due to thermal denaturation is indispensable. STUDY DESIGN/MATERIALS AND METHODS: The optical parameters in healthy porcine liver were determined in the native state and after thermal coagulation using a double integrating sphere system in the wavelength range of 400-2400 nm. RESULTS: Optical parameters showed significant fluctuations in the examined wavelength range mainly due to the water and hemoglobin content in the tissue. The greatest optical penetration depth of 7.46 mm was achieved at 1070 nm. After thermal coagulation, a clear increase in scattering and a slight decrease in absorption was found, which results in a decreased optical penetration depth. CONCLUSIONS: In order to ensure a safe and effective procedure, an adjustment of the laser power to the decreasing penetration depth is recommended during therapy. These results provide a better understanding of laser-tissue interaction and may be helpful to investigators in the field of light dosimetry in liver tissue.

Animals↗
PubMed2001

Bassini vs Lichtenstein: two basic techniques for inguinal hernia treatment.

Two techniques for inguinal hernia treatment are compared: the plastic repair of Bassini and that of Lichtenstein. The authors stress the differences between these two techniques by reporting and comparing the results obtained during four years of operating on 381 patients with the Bassini technique and 357 with the Lichtenstein technique.

Adolescent↗
PubMed2001

Inhibition of UDP-glucuronosyltransferases in rat liver microsomes by natural mutagens and carcinogens.

Eight toxic compounds of natural origin present in the human diet or used as drugs were tested as inhibitors of UDP-glucuronosyltransferase (UGT) activity in rat liver microsomes with 1-naphthol (1-NA), phenolphthalein (PPh) and 4-nitrophenol (4-NP) as substrates. Strong inhibitory effects were observed with tannic acid (tannin) and the antifungal drug griseofulvin (GF): at a concentration of 1 mM, the two compounds completely suppressed the glucuronidation of 1-NA and PPh, respectively. A concentration of 0.1 mM still proved to be highly inhibitory, and even at a concentration as low as 50 microM, tannin produced nearly 50% inhibition of 1-NA conjugation. The UGT isoforms converting 4-NP were less sensitive to the tested compounds (with the exception of GF). Kinetic studies with tannin revealed an uncompetitive type of inhibition toward 1-NA, with an apparent Ki value of 20 microM. The inhibition by GF was non-competitive with respect to PPh and was of a mixed type toward UDP-glucuronic acid, with apparent Ki values of 40 microM and 30 microM, respectively. Tannin and GF did not act as substrates for rat microsomal UGT.

Animals↗
PubMed2001

Standardized particle size for monitoring, inventory, and assessment of metals and other trace elements in sediments: <20 microm or <2 microm?

Despite the manifold factors that determine the composition of a river sediment (e.g., geology, soil type, rural or highly industrialized and densely populated, as well as forested areas, concentration of carbonates and organic matter), the linear regressions between the 9 metals determined in the fractions <2 microm and <20 microm have high coefficients (R2 after Pearson) for Cr and Cu (both 0.94), followed by Pb (0.90), Cd (0.82), Zn (0.81), Ni (0.76), and Mn (0.72). Low and very low coefficients are found for Hg (0.51) and Fe (0.22). In addition, the histograms of the metal ratios <2 microm:<20 microm (i.e. the slope of a linear regression) show that--with the exception of Cd (1.47)--all median ratios of the other metals fall within a narrow range (1.24-1.35). Both "fine" (<2 microm and <20 microm) fractions are able to fulfil the requirements for monitoring, inventory, and assessment of metals in sediments. Preference should be given to the rapid, simple, and economic <20 microm separation by sieving; this fraction corresponds fairly closely to the former suspended load of a riverine transport.

Fresh Water↗
PubMed2001

Heart luxation through a right-sided traumatic pericardial defect.

A traumatic defect of the pericardium is a rarely diagnosed entity. We present a patient with a right-sided luxation of the heart which was incidentally diagnosed during a thoracic CT performed for other reasons. Despite of the threatening strangulation of the great vessels, the patient had a stable circulation until surgical repair of the pericardial defect.

Adult↗
PubMed2001

[Problems of diagnostic assessment in low back patients].

Many different diagnostic procedures are used in patients with low back pain. Medical history and clinical examination, X-rays, computed tomography (CT)-scan, magnetic resonance imaging (MRI), diagnostic nerve root blocks and facet injections, functional tests in physiotherapy, strength tests of trunk muscles and work-related performance, and psychological and social evaluation including psychometric tests are only some of them. Despite this large number of procedures available, the scientific literature has not changed its conclusion that in about 80% of all back pain episodes the cause remains unknown. During the course of back pain episodes the relevant factors may change. The cause of the problem or the triggering factor of the pain episode may no longer be important during subacute stages, while others may be decisive for the transition to chronic stages. Thus, assessment of the cause is different from that of prognostic factors. There seems to be no consistent distribution of causes or ongoing factors in the population(s) of patients. While individual social factors may be the one important factor in one patient, functional and structural factors may be significant in another patient. Clinical examination is important, but several problems occur in the evaluation of patients with low back pain. Due to their anatomical location, important bony structures of the lumbar spine, e.g., disks or facet joints, are difficult to access by clinical examination. Additionally, there are only few diagnostic tests during clinical examination that do not rely on the patient's cooperation or communication. The term "unspecific back pain" for the majority of patients is scientifically sound, because it reflects the fact that the cause is unknown. It must be taken into consideration that this term enjoys only limited acceptance by both patients and physicians. Physicians are in charge of certifying work disability by assessing the interference of the patient's illness/disease with the specific requirements of his daily life or job. However, in clinical practice both the job tasks and the patient's abilities to perform these tasks with the given symptoms and signs is still difficult to evaluate and requires further definition.

Acute Disease↗
PubMed2001

Clinical aspects of obesity in childhood and adolescence--diagnosis, treatment and prevention.

The level of fatness at which morbidity increases is determined on an acturial basis. Direct measurements of body fat content, eg hydrodensitometry, bioimpedance or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is frequently used to define obesity clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (MC4R). Environmental/exogenous factors contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet-Biedl syndrome etc) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behavior modification and nutrition education. The role of regular exercise and exercise programs is emphasized. Surgical procedures and drugs used as treatments for adult obesity are still not recommended for children and adolescents with obesity. As obesity is the most common chronic disorder in the industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoeostasis and food intake control.

Adolescent↗
PubMed2001

Clinical aspects of obesity in childhood and adolescence.

The level of fatness of a child at which morbidity acutely and/or later in life increases is determined on an acturial basis. Direct measurements of body fat content, e.g. hydrodensitometry, bioimpedance, or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is generally accepted now to be used to define obesity in children and adolescents clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (for example, MC4R). Environmental/exogenous factors largely contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc.) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet Biedl syndrome, etc.) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasized. Surgical procedures and drugs used in adult obesity are still not generally recommended in children and adolescents with obesity. As obesity is the most common chronic disorder in industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoesostasis and food intake in relation to child health. Finally, one should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.

Adolescent↗
PubMed2001

TGF-beta 1 induces proliferation in human renal fibroblasts via induction of basic fibroblast growth factor (FGF-2).

BACKGROUND: The prognosis of primary renal disease is often dependent on the degree of tubulointerstitial scarring. Scarring is caused by proliferation and excessive matrix production of renal fibroblasts and possibly other cellular elements. Transforming growth factor-beta (TGF-beta) is the most important cytokine for the induction of matrix synthesis in the kidney. However, its effects on renal fibroblast proliferation have not been determined. We have recently demonstrated that the expression of basic fibroblast growth factor (FGF-2) is robustly up-regulated in human kidneys with tubulointerstitial fibrosis and that FGF-2 is a potent inducer of fibroblast proliferation. The present study examined the interaction between TGF-beta 1 and FGF-2 in human renal fibroblasts. METHODS: Experiments were performed on a transformed medullary fibroblast line and on primary cortical kidney and skin fibroblasts isolated from human biopsies. mRNA levels of FGF-2 and TGF-beta 1 were analyzed by Northern blot analyses. Changes in protein expression were examined by immunoblots and enzyme-linked immunosorbent assay (ELISA). Bromodeoxyuridine incorporation assays and cell counts were used to analyze cell proliferation. The expression of cell cycle-regulatory proteins cyclin-dependent kinase (cdk) 2 and the cdk inhibitor p27(kip1) were determined by immunoblots. RESULTS: Stimulation of renal fibroblasts with FGF-2 resulted in no change of TGF-beta 1 mRNA expression, whereas incubation of the cells with TGF-beta 1 induced FGF-2 mRNA up to 3.51 +/- 0.21-fold after six hours. This increase could be blocked almost completely by the addition of cyclohexamide, indicating that the process is in large part dependent on protein synthesis. The up-regulation in FGF-2 mRNA expression was paralleled by de novo detection of FGF-2 protein in the supernatant, peaking after 12 to 24 hours, as determined by Western blot and ELISA, whereas cellular protein was only increased up to 2.1-fold. Interestingly, both methods detected release of FGF-2 protein to the supernatant already at three hours, indicating a role for TGF-beta1 in directly releasing preformed FGF-2. Since TGF-beta 1 induced FGF-2, which results in fibroblast proliferation, we hypothesized that TGF-beta1 may cause fibroblast proliferation mediated by FGF-2. This hypothesis was verified by cell proliferation assays demonstrating that stimulation of renal fibroblasts with TGF-beta1 resulted in an up to 3.21 +/- 0.28-fold increase in bromodeoxyuridine incorporation and a 1.95 +/- 0.16-fold increase in cell number after 72 hours. This mitogenic effect of TGF-beta1 could be blocked completely by the addition of a neutralizing antibody to FGF-2 or the tyrosine kinase inhibitor tyrphostin AG1296, which blocks FGF receptor (FGFR) tyrosine kinase activity. Conversely, a neutralizing antibody to epidermal growth factor (EGF) or the tyrphostin B42, which inhibits EGF receptor signal transduction, had no effect. Interestingly, a neutralizing antibody to PDGF had only minor effects in primary kidney fibroblasts but reduced TGF-beta 1-induced proliferation considerably in primary skin fibroblasts. Finally, TGF-beta1-induced proliferation in kidney fibroblasts was paralleled by a robust increase in cdk 2 protein expression up to 72 hours, whereas p27(kip1), whose activity is maintained by TGF-beta in epithelial cells, was down-regulated up to 48 hours. CONCLUSIONS: Our studies demonstrate, to our knowledge for the first time, that TGF-beta1 induces proliferation in human renal fibroblasts and that this process is mediated largely by FGF-2. The induction of proliferation by TGF-beta 1 via induction of FGF-2 may play an important role in the autonomy of renal fibroblast growth and thus in the pathogenesis of human fibrogenesis.

CDC2-CDC28 Kinases↗
PubMed2001

Dynamic changes of atrial septal defect area: new insights by three-dimensional volume-rendered echocardiography with high temporal resolution.

AIMS: The purpose of this study was: (i) to record dynamic changes in the area of atrial septal defects (ASD) during a cardiac cycle, and (ii) to investigate factors which influence ASD dynamics. Implementation of new software modifications allowed the frame rate to be doubled, as compared to usual techniques. METHODS AND RESULTS: Twenty patients were examined using transoesophageal three-dimensional (3D) echocardiography. In 10 patients the 3D dataset was recorded with a frame rate of 25Hz, in another 10 patients with a frame rate of 50Hz. The ASD area was planimetried for each picture and the changes analysed over time. The ASD area showed dynamic changes during the cardiac cycle with an end-systolic maximum and end-diastolic minimum. The influence of the various phases of the cardiac cycle on area changes could be differentiated especially at higher temporal resolution. The relative change in ASD area showed no significant relationship to Q(p)/Q(s)ratio, mean ASD size or heart rate. By contrast, there was a slight inverse correlation to age (r=-0.t45,P <0.05). CONCLUSION: Transoesophageal 3D volume-rendered echocardiography permits quantitative recording of ASD dynamics. The ASD area changes are influenced especially by the various phases of the cardiac cycle.

Adolescent↗