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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 595 records · Page 33Linked to original sources
PubMed1998

T1 effects of a bolus-injectable superparamagnetic iron oxide, SH U 555 A: dependence on field strength and plasma concentration--preliminary clinical experience with dynamic T1-weighted MR imaging.

PURPOSE: To investigate the field strength dependency of relaxivity values with SH U 555 A, concentration-dependent T1 effects, and findings at dynamic T1-weighted magnetic resonance (MR) imaging in patients with focal liver lesions. MATERIALS AND METHODS: Longitudinal relaxivity (r1) with SH U 555 A was measured in human plasma (0.02-300.00 MHz), and transverse relaxivity (r2) was measured at 10, 20, and 40 MHz. Second, a dilution series in human plasma was used at 1-T, T1-weighted, spin-echo or fast low-angle shot (FLASH) imaging. In 22 patients with focal liver lesions, imaging with the latter sequence was performed with a dose of SH U 555 A of 10 mumol Fe/kg. RESULTS: The r1 of SH U 555 A decreased with increasing field strength, but was higher at high field strengths than r1 values for gadolinium chelates. Enhancement calculations for different iron concentrations in human plasma demonstrated positive enhancement at concentrations less than 700 mumol Fe/L. Enhancement increased with the degree of T1 weighting and was highest for the FLASH sequence with the shortest TE (+81.4% with 300 mumol Fe/L). Enhancement was positive in the liver for at least 30 seconds and in the spleen for at least 480 seconds. CONCLUSION: Signal intensity changes at dynamic T1-weighted MR imaging after bolus injection of SH U 555 A can be explained by dynamic changes in iron-plasma concentration.

Contrast Media↗
PubMed1998

Minimal influence of blood flow on interstitial glucose and lactate-normal and insulin-resistant muscle.

To study the regulation of the interstitial glucose concentration in skeletal muscle, nine control subjects and nine older and overweight non-insulin-dependent diabetes mellitus (NIDDM) subjects with extreme insulin resistance were investigated with microdialysis in the medial femoral muscle before and during a euglycemic insulin clamp. After an overnight fast, arterial plasma glucose concentration was 4.9 +/- 0.1 and 8.5 +/- 0.6 mmol/l (P < 0.001), respectively. The arterial-interstitial concentration ([a-i]) differences of glucose and lactate were 0.43 +/- 0.16 (P < 0.05) and -0.13 +/- 0.05 mmol/l, respectively, in normal subjects. In NIDDM subjects, [a-i] differences for glucose and lactate were nonsignificant. Muscle blood flow was similar in controls and NIDDM subjects. During the glucose clamp, the glucose [a-i] differences increased and the lactate [a-i] differences decreased significantly in both groups. The glucose 170 infusion rate was 8.0 +/- 0.77 vs. 3.2 +/- 0.51 mg.kg-1.min-1 (P < 0.001), and blood flow was 9.9 +/- 1.6 vs. 6.7 +/- 0.9 ml.100 g-1.min-1 (P < 0.05) in controls and NIDDM subjects, respectively. These results show that 1) the capillary wall is rate limiting for muscle glucose uptake and lactate release in control subjects but not in postabsorptive hyperglycemic insulin-resistant subjects, 2) vasodilation during insulin infusion does not prevent the increase in [a-i] difference of glucose in normal subjects, and 3) in severely insulin-resistant muscle, the [a-i] difference of glucose is not extended despite lack of vasodilation.

Adult↗
PubMed1998

Correction of the TNF-LT alpha-deficient phenotype by bone marrow transplantation.

Mice with inactivated TNF-LT alpha genes have profound abnormalities of the immune system with hypoimmunoglobulinaemia, lack of lymph nodes, undifferentiated spleen, and defective Ig class switch. Transplantation of bone marrow cells from wild-type mice restored the synthesis of TNF, corrected the splenic microarchitecture, repopulated the lamina propria with IgA-producing plasma cells, and normalized the serum immunoglobulin levels of TNF-LT alpha deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell-dependent antigen is corrected. These data demonstrate that most TNF-producing cells are bone-marrow-derived, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow, cell transplantation.

Animals↗
PubMed1998

Intravesical treatment of bladder cancer: current problems and needs.

Especially in patients with superficial bladder cancer being at risk of tumor progression, therapeutic or adjuvant treatment concepts are required. Based upon experimental trials and clinical case reports, intravesical immunotherapy has been developed and further refined in many prospective studies through the last 25 years. Supported by the results of several phase III trials, today instillation therapy with Bacille bilié de Calmette-Guérin (BCG) is accepted as standard therapeutic intervention in carcinoma in situ of the bladder and for prophylaxis of tumor recurrence in superficial, bladder cancer. Current protocols are aiming at the determination of the optimal dosage and regimen and the investigation of the impact of BCG therapy on tumor progression. Furthermore, there is significant clinical need to identify factors predicting the outcome of BCG therapy in a given patient. Based upon the promising results of BCG therapy, several cytokines have been investigated, specifically in order to decrease the side effects of BCG. However, despite of some efficacy and lower side effects, other forms of immunotherapy, e.g., interferon, interleukin 2, or keyhole limpet hemocyanin, must still be regarded as experimental and need further investigation.

Administration, Intravesical↗
PubMed1998

An unexpected complicationof the remote-controlled intraurethral valve pump for urinary incontinence.

We report an unexpected complication of the remote-controlled intraurethral valve pump in a patient with neurogenic bladder. A meningomyelocele patient with an atonic bladder received an intraurethral valve pump. Acute urinary retention was caused by a mucus clot obstructing the pump. Prior to extended clinical use, the remote-controlled intraurethral valve pump should be evaluated in prospective multicenter studies.

Acute Disease↗
PubMed1998

Mineralocorticoid receptor also modulates basal activity of hypothalamus-pituitary-adrenocortical system in humans.

Hippocampal mineralocorticoid (MRs) and glucocorticoid receptors (GRs) have been demonstrated to regulate the activity of the hypothalamus-pituitary-adrenocortical (HPA) system. To elucidate the role of the hippocampal MR in the circadian activity of the human HPA system, we studied diurnal secretory profiles of corticotropin (ACTH) and cortisol in 10 healthy male humans before and after an 8-day treatment with the MR antagonist spironolactone. 24-hour blood sampling at 30-min intervals was performed for estimation of cortisol (q30) and ACTH (q120). Saliva cortisol was measured for estimation of unbound cortisol. At the end of the 24-hour sampling period a corticotropin-releasing hormone (CRH) challenge was performed. High plasma concentrations of the active metabolite canrenone were achieved (begin of sampling: 2,653 +/- 693 nmol/l; end of sampling: 747 +/- 177 nmol/l). There was a significant increase in the diurnal minima (37.1 +/- 13.3 vs. 23.7 +/- 8.9 nmol/l, p < 0.02) and mean cortisol (193.5 +/- 25.8 vs. 173.0 +/- 23. 0 nmol/l, p < 0.03) plasma concentrations. However, the diurnal peak concentrations and pulsatile secretory features were unchanged after spironolactone treatment. For saliva cortisol, the only significant treatment difference was a decrease in the diurnal amplitude of cortisol relative to the diurnal mean concentration (2.56 +/- 0.47 vs. 3.11 +/- 0.87, p < 0.03). After spironolactone treatment there was a decrease in diurnal mean ACTH concentrations (46.2 +/- 14.4 vs. 41.8 +/- 10.3 pmol/l). There was no difference in the ACTH and cortisol response after infusion of CRH before and after spironolactone treatment. CBG plasma concentrations were significantly increased (22.4 +/- 2.3 vs. 19.2 +/- 2.7 mg/l, p < 0. 01) after spironolactone treatment, which possibly contributed to the observed increase in plasma cortisol. In summary, as predicted from animal studies we found significant effects of MR antagonization to be restricted to time windows of low HPA system activity. These findings are similar to the effects of aging upon the HPA system. However, the effect of spironolactone treatment was small, suggesting that the HPA system activity in humans is modulated but not regulated by the hippocampal MR.

Adrenal Cortex↗
PubMed1998

Dental health status and endodontic treatment of captive brown bears (Ursus arctos ssp.) living in the Bernese bear pit.

The teeth of five adult captive brown bears (Ursus arctos ssp.) were examined and radiographed for occlusion, loss of teeth, dental plaque and calculus, and attrition under general anesthesia. Deposits of dental calculus were found in various locations with an overall prevalence of 8% to 15% of all tooth surfaces. In all five animals, severe enamel and dentinal attrition defects were observed in canine teeth with exposed pulp. Cage-chewing behavior is probably the main cause for the dental attrition. The composition of the food and feeding management are most likely responsible for the lack of natural cleaning and the resulting plaque and calculus formation. All affected canine teeth were treated with endodontic procedures using several materials and techniques, and evaluated one- to two-and-a-half years later by clinical examination, radiography, and scanning electron microscopy of silicone casts of the treated teeth. All coronal fillings were tight. The apices were not completely sealed in two teeth. We conclude that the use of adequate and specialized instrumentation and techniques for the treatment of these long, curved, large diameter root canals is more important than the particular endodontic and restorative materials used. The dental health status of zoo animals is an indicator of their general well-being. Preventive measures should be taken in their environment and management to minimize the risk of dental conditions.

Animals↗
PubMed1998

Loss of immunoreactivity for RTI40, a type I cell-specific protein in the alveolar epithelium of rat lungs with bleomycin-induced fibrosis.

After lung injury, the epithelial cells lining the alveolar surface in rat lung show an altered distribution of several membrane proteins. Pulmonary fibrosis was induced by intratracheal administration of bleomycin into the lung of rats and the distribution of RTI40, a recently detected alveolar epithelial type I cell antigen, was examined, as well as the relationship between RTI40 and a type I cell-specific antigen recognized by the monoclonal antibody MEP-1 and the type I cell-binding lectin Bauhinia purpurea in serial sections and double stainings. Loss of RTI40 protein was observed in fibrotic lungs, particularly in areas with obliteration of alveoli. Pre-embedding immunoelectron microscopy confirmed this observation by detection of RTI40 protein in the alveolar lumen. Western blot analysis revealed elevated levels of RTI40 in the bronchoalveolar fluid of bleomycin-treated rats with a maximum at day 7 after treatment. Twenty-eight days after bleomycin application, the bronchoalveolar fluid contained three times the amount of RTI40 x mg protein(-1) of control lungs, as determined by semiquantitative dot blot. These results suggest RTI40 as a tool for the evaluation of alveolar epithelial type I cell behaviour during re-epithelialization processes.

Animals↗
PubMed1998

The average dose-area product at intravenous urography in 205 adults.

The intravenous urography (IVU) is the most important and most frequently performed radiological examination in urology. This prospective study determined the dose-area product as a measurement of radiation dose in 205 adult patients undergoing IVU. Average dose-area product was 1017 cGy cm2. An average 3.7 radiographs were obtained per patient. Tomographic views were required in only 8.8% of cases. Radiation dose is dependent not only on the number and size of the obtained radiographs, but on the physical constitution of the patient. The dose-area products measured show a clear relationship to the body weight of the patient.

Adolescent↗
PubMed1998

Changes in bone turnover induced by aerobic and anaerobic exercise in young males.

Physical activity is considered an important factor in attaining bone mass. However, the mechanisms by which exercise affects bone metabolism are not completely understood. The present study was performed to investigate the effects of aerobic and anaerobic exercise on bone turnover. Twenty healthy young males (aged 20-29 years) were followed through an 8-week program of aerobic (n = 10) and anaerobic training (n = 10). Ten age-matched individuals served as controls. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcin (OC), and urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined as indices of bone metabolism. After 4 weeks of aerobic training, serum BAP and OC (p < 0.01), and urinary Pyd (p < 0.001) and Dpd (p < 0.01) were significantly reduced. After 8 weeks, BAP and OC levels had returned to baseline values, whereas the urinary cross-link excretion remained low. In the anaerobic training group, elevated levels of BAP (p < 0.05 vs. week 4), OC (p < 0.05 vs. week 4), and Pyd (p < 0. 01 vs. week 0) were observed after 8 weeks of exercise. Changes in urinary Pyd and Dpd (week 0 vs. week 8) were positively correlated with changes in the mean power level in the Wingate test, a parameter of the anaerobic performance capacity (r = 0.50 and r = 0. 55, p < 0.01, respectively). In the controls, no significant changes in biochemical markers were observed. We conclude that aerobic and anaerobic training excert different effects on bone metabolism. While aerobic training led to changes compatible with reduced bone resorption activity, anaerobic training seems to result in an overall accelerated bone turnover. Therefore, the impact of physical activity on bone turnover may depend on the kind of exercise performed.

Adult↗
PubMed1998

Immunological and functional analyses of the extracellular domain of human tissue factor.

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation via formation of an enzymatic complex with coagulation factor VII/VIIa (FVII/VIIa). Although FVII is the only known ligand for TF, several reports in recent years have shown that the function of TF may not be limited to serving as a trigger of coagulation but that TF could also play a role in cellular signaling, metastasis, adhesion and embryogenesis. To explore the loci of the extracellular domain of TF important for its function, we analyzed the functional and immunological epitopes of TF1-219 by the use of both E. coli expressed TF variants encompassing various portions of the extracellular domain of TF and different anti-TF monoclonal antibodies (mAbs). N- and C-terminally truncated TF variants were analyzed for their VIIa-dependent procoagulant activity (PCA). The results obtained are in agreement with previously performed mutant and structural analyses of the interaction of FVII/FVIIa with the extracellular domain of TF. In addition, we observed that combination of two TF variants, Ec-TF1-122 and Ec-TF120-219, yields a soluble and active two-chain TF molecule with remarkable PCA. The reaction patterns of anti-TF mAbs with truncated TF variants and synthetic TF-derived peptides demonstrated that at least three distinct conformation-dependent epitope areas of TF (residues 1-25, 175-202, and 181 -214, respectively) are detected by these mAbs raised against native TF. In fact, mAbs, which are directed to the same epitope area of TF, behave very similar in various applications including immunohistochemistry and clotting tests. Since mAbs directed to the C-terminal epitope area of TF (residues 181-214) influence TF activity independent of FVIIa-binding, this region may be involved in functions of TF distinct from haemostasis.

Antibodies, Monoclonal↗
PubMed1998

Transgenic approaches to the increase of disease resistance in farm animals.

Molecular genetics and reproductive biology techniques enable the transfer of foreign DNA into mammals. Novel approaches to modify disease resistance or susceptibility in livestock are justified by economic and animal welfare concerns. Current research on the improvement of disease resistance by gene transfer focuses on three main strategies, as follows: a) somatic gene transfer, i.e., nucleic acid vaccines b) deletive germ-line gene transfer, i.e., gene knockout c) additive germ-line gene transfer. These strategies aim at either the transient or stable expression of components known to influence non-specific or specific host defence mechanisms, or the disruption of genes known to cause susceptibility to disease. Referring to the source of the effective agent and the site and mode of action, the strategies are termed 'genetic', 'congenital', 'intracellular' and 'extracellular' immunisation. Each gene transfer experiment has to be evaluated carefully with respect to the potential to create novel cases of pathogen resistance or to lose species barriers or cell-type restrictions.

Animals↗
PubMed1998

Drug distribution. The forgotten relative in clinical pharmacokinetics.

The target concentration strategy has proved a valuable approach for dose individualisation, giving proper weight to the high interindividual variation in plasma concentrations. Nevertheless, optimisation of plasma concentrations does not necessarily yield optimal pharmacodynamic effects because variability in the plasma concentration-effect relationship is far from insignificant. We argue that this is due not only to unpredictable target tissue sensitivity but also to a highly variable, and equally unpredictable, distribution process from plasma into the interstitial space of the target tissue, the true effect compartment. This is borne out by recent results from studies employing modern techniques that enable direct measurement of target tissue drug concentrations, like magnetic resonance spectroscopy, single photon emission computed tomography, and tissue microdialysis. Such forthcoming results highlight the importance of the distribution process as a key factor determining drug response. Clinical pharmacology should seek an improved understanding of the biological determinants governing not only plasma but tissue drug concentrations.

Biological Availability↗
PubMed1998

Potential of autologous immunologic effector cells for prediction of progression of disease in patients with chronic myelogenous leukemia.

In autologous bone marrow transplantation, immunologic effector cells such as lymphokine activated killer (LAK) cells may be useful for purging of bone marrow since these cells might have an additional in vivo effect on tumor cells in contrast to other purging protocols. Recently, immunologic effector cells termed cytokine-induced killer (CIK) cells have been shown to be more useful than LAK cells for purging of autologous BM in the context of autologous BMT. Here, we show that the expression of bcr/abl in CIK cells generated from patients with CML correlates with progression of disease in individual patients. In addition, progression of disease from chronic phase to accelerated phase could be predicted in two patients by studying the expression of bcr/abl in CIK cells generated from CML patients. Thus, it might be possible to use CIK cell generation for the prediction of progression of disease in CML patients.

Adult↗
PubMed1998

Antitumor activity of a PKC-alpha antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted into nude mice.

A 20-mer phosphorothioate oligodeoxynucleotide (ODN) directed against human protein kinase C-alpha (CGP 64128A = ISIS 3521) was analyzed for its antitumor activity either alone or in combination therapy. Combination studies with CGP 64128A and standard chemotherapeutic agents (cisplatin, mitomycin-C, vinblastine, estracyt and adriamycin) were performed in nude mice that had been transplanted s.c. with a variety of human tumors (breast, prostate, large cell lung and small cell lung carcinomas, and melanomas). Additive antitumor effects with CGP 64128A and the cytotoxins were found for half of the combinations studied. The combination of CGP 64128A with vinblastine or cisplatin showed superadditive antitumor activities against MCF-7 human breast carcinomas and PC3 prostate carcinomas with complete responses. CGP 64128A in combination with adriamycin resulted in superadditive antitumor effects against BT20 human breast carcinomas with complete tumor responses, and in combination with mitomycin-C superadditive antitumor effects with cures were observed against NCI-H460 human large cell carcinomas. The antitumor activity of CGP 64128A appeared to be due to a sequence-dependent mechanism of action as two 20-mer control ODNs were completely inactive as single agents against A549 and NCI-H69 human lung carcinomas. The antitumor activity of cisplatin against NCI-H69 human small cell lung carcinomas was slightly inhibited by one of the control ODNs, indicating that the superadditive antitumor activities of CGP 64128A in combination with cisplatin are the result of a sequence-dependent mechanism of action.

Animals↗
PubMed1998

Influence of the angiographic internal carotid artery stenosis assessment method on indicating carotid surgery.

BACKGROUND: To estimate the influence of different kinds of angiographic internal carotid artery (ICA) stenosis assessment methods on clinical decision making on carotid surgery. METHOD: One hundred angiographically proven ICA lesions in 65 patients (54 men, 11 women, mean age +/- SD, 64 +/- 8 years) were evaluated by simultaneous biplane angiography. The angiograms were analyzed using three kinds of linear diameter reduction methods [North American (NASCET), and European (ECST) carotid surgery trial method, common carotid artery method (CC)], and five area reduction methods reflecting more accurately the anatomical degree of stenosis [squared NASCET, ECST and CC (N2, E2, CC2), combined stenosis estimation of two projections (NASCET-bi, ECST-bi)]. All lesions were additionally evaluated by continuous wave (cw-)Doppler ultrasound prior to angiography. Between method agreement on classifying the lesions into stenosis < 70% and into stenosis > or = 70% was calculated by means of kappa statistic. RESULTS: The degree of stenosis (median and inter-quartile range) ranged between 65% (38-82) by means of NASCET and 91% (87-93) by means of CC2. Thirty-seven ICA stenoses would have been operated on using NASCET, but 82 using CC2. Between method agreement on assessing high grade ICA stenosis ranged from poor (kappa value 0.17 for the pair NASCET/CC2) to excellent (kappa value 0.92 for the pair N2/NASCET-bi). Cw-Doppler ultrasound showed a good agreement (kappa value 0.72-0.80) with all angiographic methods using an area reduction formula apart from CC2. The agreement was moderate between cw-Doppler and NASCET and ECST, respectively. CONCLUSION: The clinical decision to operate on an ICA stenosis will strongly be influenced by the angiographic method used. Because reliable clinical data exist only for the NASCET and ECST method these two angiographic stenosis assessment method should be used for clinical decision making.

Aged↗
PubMed1998

Alteration of cerebral blood flow in patients with bacterial and viral meningoencephalitis.

PURPOSE: Our purpose was to investigate cerebral blood flow disturbances in patients with bacterial and viral meningoencephalitis. METHODS: Forty-two patients with acute bacterial and viral meningoencephalitis and 14 control subjects were studied using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). SPECT images were evaluated semiquantitatively. The results were compared with clinical severity of the meningoencephalitis assessed at the time of the SPECT study with the Hunt and Hess scale, with separately recorded focal clinical signs, and with the Glasgow outcome scale (GOS) after 3 weeks. RESULTS: Count density values were significantly reduced in patients with bacterial meningoencephalitis as compared with the control subjects. Inhomogeneous tracer accumulation assessed by asymmetry indexes was significantly greater in patients than in the control group. With increasing Hunt and Hess scores, the count density values decreased and the asymmetry indexes increased. Patients with a poor outcome (GOS 1 to 3) had significantly higher asymmetry indexes and lower CDV values than did patients with a good outcome. CONCLUSION: Global and focal alterations of cerebral perfusion are frequent in bacterial and viral meningoencephalitis and correlate with acute clinical state.

Adult↗