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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 55 records · Page 3Linked to original sources
PubMed2001

41Ca ultratrace determination with isotopic selectivity > 10(12) by diode-laser-based RIMS.

41Ca ultratrace determination by diode-laser-based resonance ionization mass spectrometry with extremely high isotopic selectivity is presented. Application to environmental dosimetry of nuclear reactor components, to cosmochemical investigations of production cross sections, and biomedical isotope-tracer studies of human calcium kinetics are discussed. Future investigations are possible use in 41Ca-radiodating. Depending on the application, 41Ca isotopic abundances in the range of 10(-9) to 10(-15) relative to the dominant stable isotope 40Ca must be determined. Either double- or triple-resonance optical excitation with narrow-band extended cavity diode lasers and subsequent non-resonant photoionization of calcium in a collimated atomic beam were used. The resulting photoions are detected with a quadrupole mass spectrometer optimized for background reduction and neighboring mass suppression. Applying the full triple-resonance scheme provides a selectivity of approximately 5 x 10(12) in the suppression of neighboring isotopes and > 10(8) for isobars, together with an overall detection efficiency of approximately 5 x 10(-5). Measurements on a variety of sample types are discussed; the accuracy and reproducibility of the resulting 41Ca/40Ca isotope ratios was better than 5%.

Calcium Radioisotopes↗
PubMed2001

Percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas.

The objective of this study was to evaluate the sensitivity and specificity of percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. In a 1-year period 158 image-guided percutaneous core-needle biopsies of enlarged lymph nodes were performed on 149 consecutive patients using a Tru-cut needle fired by a biopsy gun. In 135 cases the biopsy findings could be confirmed by histologic examination of additional tissue samples (n = 59) or by correlation with the patient's clinical and radiologic course (n = 76). The final diagnoses were malignant lymphoma in 65 cases, leukemic nodal infiltration in 2, nodal metastases from a solid tumor in 37 and benign changes or no evidence of malignancy in 31 cases. The core-needle biopsies correctly diagnosed 58 of 65 malignant lymphomas, corresponding to a sensitivity of 89% and a specificity of 97%. Fifty-five of the 58 (95%) correctly diagnosed malignant lymphomas could be subclassified on the basis of the core-needle biopsy. Image-guided core-needle biopsy of enlarged lymph nodes with a Tru-cut needle is a useful method for the diagnosis and subclassification of malignant lymphomas.

Adolescent↗
PubMed2001

The value of desoxypyridinoline in the diagnostics of loosened arthroplasty.

According to several reports in the last few years, desoxypyridinoline (Dpd) in urine increases significantly in cases of loosened arthroplasty. Therefore, this marker was suggested as useful in the diagnostics of implant loosening. In this study, the level of Dpd was determined in 69 patients with arthroplasty of the hip or the knee joint. Thirty-four of these patients received revision surgery following implant loosening. In 35 of these 69 patients, there were no clinical or radiological signs of loosening (control group). The mean age of the patients with loosened implants (22 women, 13 men) was 67.9 years and of the control group (22 women, 12 men) 66.9 years. In the group with arthroplastic loosening, as well as in the control group, 14 patients had increased levels of Dpd. There were 20 patients in the group with loosened arthroplasty and 19 patients in the control group that had normal levels of Dpd. The female patients had a mean Dpd level of 8.6 nmol/mmol creatinine (4.3-24 nmol/mmol creatinine) in the urine in cases of loosening and 10.1 nmol/mmol creatinine (2-33 nmol/mmol creatinine) in the control group. The male patients had a mean Dpd level of 7.8 nmol/mmol creatinine (3.2-19.2 nmol/mmol creatinine) in the urine in cases of loosening and 5.8 nmol/mmol creatinine (0.3-11.7 nmol/mmol creatinine) in the control group. In conclusion there was no significant increase in Dpd in patients with implant loosening compared with the control group. Furthermore, older patients often suffer from diseases causing increased bone resorption that may falsify the test results. We cannot confirm that Dpd is helpful in the diagnostics and screening of implant loosening.

Adult↗
PubMed2001

Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras.

Mutation of the K-ras gene is thought to be an early and important event in pancreatic carcinogenesis. In order to study the role of this molecular alteration in the transition from the normal to the neoplastic pancreatic cell, bovine pancreatic duct cells were first immortalized by SV40 large T antigen (Ag) complementary (c)DNA transfection and then transfected with a mutated K-ras gene. As did primary duct cells, the immortalized duct cells (more than 100 passages) expressed cytokeratins, carbonic anhydrase type-II, cystic fibrosis transmembrane conductance regulator (CFTR), and multidrug resistance (mdr). They grew as a single layer after transplantation under plastic domes and formed three-dimensional structures resembling ducts when grown on Matrigel. Cell growth was stimulated by insulin, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, but cells did not respond to gastrin and CCK-8. They did not form colonies in soft agar nor did they form tumors in nude mice. Immortalized cells transfected with mutated K-ras acquired the ability to form tumors after orthotopic injection into the nude mouse pancreas. It is concluded that SV 40 immortalized bovine pancreatic

Animals↗
PubMed2001

Intraoperative radiofrequency maze ablation for atrial fibrillation: the Berlin modification.

BACKGROUND: The Cox-maze procedure combined with an operation for organic heart disease is highly successful in the elimination of chronic atrial fibrillation. However, it prolongs significantly the aortic cross-clamp and operating time. In this study, a simplified left atrial maze procedure, which is a short procedure performed using a surgical radiofrequency ablation probe, is added to elective open heart procedures in patients with atrial fibrillation. METHODS: Forty-eight adults with atrial fibrillation (duration, 6 months to 36 years) underwent elective open heart operations (isolated valve procedures or coronary artery bypass grafting, n = 27 patients; combined procedures, n = 21 patients) combined with intraoperative radiofrequency ablation of the left atrium. The postoperative follow-up period ranged from 1 to 11 months (mean, 4 months). Possible predictors for persistent postoperative atrial fibrillation were determined among 40 variables by univariate and multivariate analyses. RESULTS: Intraoperative radiofrequency ablation prolonged the aortic cross-clamp time for 6 to 14 minutes (mean, 11 minutes). Freedom from atrial fibrillation was 100% intraoperatively, 25% at 1 week after operation (12 of 48 patients), 59% at 1 month postoperatively (16 of 27 patients), 64% at 3 months postoperatively (16 of 25 patients), and 92% at 6 months postoperatively (12 of 13 patients). The only predictor of postoperative atrial fibrillation was the presence of coronary artery disease (odds ratio, 7.5; 80% confidence interval, 2.24-25.13). CONCLUSIONS: Intraoperative radiofrequency ablation of the left atrium combined with an operation for organic heart disease effectively eliminates atrial fibrillation without significant prolongation of the aortic cross-clamp and operative time. The presence of coronary artery disease decreases the success rate during the first 6 postoperative months.

Adult↗
PubMed2001

Dynamics of membrane penetration of the fluorescent 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group attached to an acyl chain of phosphatidylcholine.

Location and dynamic reorientation of the fluorophore 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) covalently attached to a short (C6) or a long (C12) sn2 acyl chain of a phosphatidylcholine molecule was investigated by fluorescence and solid-state NMR spectroscopy. 2H NMR lipid chain order parameters indicate a perturbation of the phospholipid packing density in the presence of NBD. Specifically, a decrease of molecular order was found for acyl chain segments of the lower, more hydrophobic region. Molecular collision probabilities determined by 1H magic angle spinning nuclear Overhauser enhancement spectroscopy indicate a highly dynamic reorientation of the probe in the membrane due to thermal fluctuations. A broad distribution of the fluorophore in the lipid bilayer is observed with a preferential location in the upper acyl chain/glycerol region. The distribution of the NBD group in the membrane is quite similar for both the long- and the short-chain analog. However, a slight preference of the NBD group for the lipid-water interface is found for C12-NBD-PC in comparison with C6-NBD-PC. Indeed, as shown by dithionite fluorescence assay, the long-chain analog reacts more favorably with dithionite, indicating a better accessibility of the probe by dithionite present in the aqueous phase. Forces determining the location of the fluorophore in the lipid water interface are discussed.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Development of a molecular diagnosis assay based on electrohybridization at plastic electrodes and subsequent PCR.

Technologies enabling specific recognition of medically relevant nucleic acid sequences will play a pivotal role in future medical diagnosis. Whereas many approaches to molecular diagnosis systems include DNA microarrays on chips and fluorometric detection, the basis of our approach is the use of inexpensive components like plastic or metal thin film electrodes with low multiplexing and an electrochemical detection unit. To increase the sensitivity, PCR can be used as an intermediate step. For selective enrichment, specific nucleic acid probes were covalently attached at their 5'-ends to conducting polycarbonate/carbon fiber electrodes. Complementary oligonucleotides were enriched at the electrodes by cyclic inversion of an electrochemical potential, transferred into a PCR vial and thermally or electrochemically desorbed. The analysis of the PCR product shows the efficiency and selectivity of the electrochemical enrichment. Hybridization of DNA was shown by electrochemical methods, in this work especially by differential pulse voltammetry (DPV) using the single strand specific hybridization redox indicator osmium(VIII)-tetroxide, and potentiometric stripping analysis (PSA). This combination of experimental methods is the basis for a molecular diagnosis system including a disposable nucleic acid modified working electrode for specific enrichment, detection and quantification, and an optional capillary PCR module for fast amplification.

Biosensing Techniques↗
PubMed2001

Patients' and relatives' assessment of clozapine treatment.

BACKGROUND: Subjective evaluations by schizophrenic patients and their relatives of clozapine treatment were assessed as part of an exploratory study. METHODS: A problem-centred interview was carried out with 80 patients at discharge from in-patient or day-hospital treatment. Views of 46 relatives on the treatment were also assessed. RESULTS: In addition to expected effects (improvement of or stabilisation of one's state of mental health, antipsychotic effects), patients surprisingly often highlighted the calming and relaxing effect of clozapine as well as improved sleep as particularly positive. While more than half of the respondents expected a worsening of their condition if they stopped taking medication, only every fifth patient feared a relapse. Among the negative effects, fatigue and sedation were cited by far the most often. The absence of extrapyramidal side effects was clearly noted as an advantage of clozapine. Only 10% of those questioned were aware of the risks for the haemotopoetic system associated with the drug. Differences were found between patients' and relatives' assessments particularly with regard to the negative effects. CONCLUSIONS: Patients and relatives frequently hold specific and distinct views on clozapine treatment. These views should be considered when patients and relatives are informed and when compliance is addressed.

Adult↗
PubMed2001

Vesicular and nonvesicular transport of phosphatidylcholine in polarized HepG2 cells.

We have investigated the transport and canalicular enrichment of fluorescent phosphatidylcholine (PC) in HepG2 cells using the fluorescent analogs of PC C6-NBD-PC and beta-BODIPY-PC. Fluorescent PC was efficiently transported to the biliary canaliculus (BC) and became enriched on the lumenal side of the canalicular membrane as shown for C6-NBD-PC. Some fluorescent PC was transported in vesicles to a subapical compartment (SAC) or apical recycling compartment (ARC) in polarized HepG2 cells as shown by colocalization with fluorescent sphingomyelin (C6-NBD-SM) and fluorescent transferrin, respectively. Extensive trafficking of vesicles containing fluorescent PC between the basolateral domain, the SAC/ARC and the BC as well as endocytosis of PC analogs from the canalicular membrane were found. Evidence for nonvesicular transport included enrichment of the PC-analog beta-BODIPY-PC in the BC (t1/2 = 3.54 min) prior to its accumulation in the SAC/ARC (t1/2 = 18.5 min) at 37 degrees C. Transport of fluorescent PC to the canalicular membrane also continued after disruption of the actin or microtubule cytoskeleton and at 2 degrees C. These results indicate that: (i) a nonvesicular transport pathway significantly contributes to the canalicular enrichment of PC in hepatocytic cells, and (ii) vesicular transport of fluorescent PC occurs from both membrane domains via the SAC/ARC.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease: a prospective study in more than 100 patients.

The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato-biliary disease. We investigated 118 consecutive patients, aged 24-89 with the following clinical diagnoses: choledocho/cholecystolithiasis (28), cholangiocellular carcinoma (21), gall bladder tumor (8), liver metastasis (3), autoimmune disease (8), chronic pancreatitis (16), pancreatic carcinoma (11), papillary disease (4), hepatic cirrhosis (6), cholangitis (2), anomalies (2), and normal (9). Bile was aspirated during routine endoscopic retrograde cholangio pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). DNA was prepared freshly from a native aliquot. p53 mutations were detected by polymerase chain reaction (PCR) for exons 5 through 8 followed by TGGE. PCR for ras mutations was performed as RFLP-PCR with sequencing. In four cases, mutations in p53 could be found in exons 6 and 7. Twenty-two samples showed ras mutations; ras mutations were found in choledocholithiasis (4/28), bile duct (5/21), gall bladder (3/8) and pancreatic (1/11) carcinoma, liver metastasis (3/3), ulcerative colitis (2/3), PSC (1/2), and chronic pancreatitis (1/16). Cytology was clearly positive in seven cases, suspicious in three other, inconclusive in six, and negative in the rest. The molecular analysis resulted in a sensitivity of 33% and specificity of 87%, respectively, for the diagnosis of a malignant condition. PCR for p53 and ras mutations may aid the diagnosis of primary and secondary (metastatic) hepatobiliary disease if a malignant condition of the bile ducts and the liver is suspected and cytology is inconclusive or negative. However, the incidence of p53 and ras mutations in bile seems less frequent than in other malignant conditions of the gastrointestinal tract and the pancreas and lower than in tissue, leaving a poor sensitivity and specificity. Nevertheless, the presence of a p53 and/or ras mutation per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or inconclusive.

Adult↗
PubMed2001

[Etiology of schizophrenia from the viewpoint of family].

OBJECTIVE: In a former quantitative study on relatives' beliefs about the causes of functional psychoses a preference for psychosocial explanations was found. There were also indications of an inclination towards a multicausal concept. The aim of this study is to try to replicate these findings using semi-qualitative methods. In addition, we are interested in knowing to what extent the causal beliefs of relatives are similar to those of the patients. METHOD: Problem-centered interviews were conducted with 31 relatives of schizophrenic patients. A computer-assisted qualitative content analysis was carried out with the transcripts of the interviews. RESULTS: As in the previous study, relatives showed a strong propendency to endorse psychosocial explanations. However, among only one third a multicausal concept could be observed. The causal beliefs of relatives and patients were quite similar. DISCUSSION: The findings are discussed with reference to the concept of subjective illness theory and the concept of social representations.

Adult↗
PubMed2001

[Etiology of schizophrenia from the viewpoint of the patient].

OBJECTIVE: According to a quantitative study on causal beliefs patients with functional psychoses favour psychosocial over biological explanations. They also tend to endorse a multicausal concept. The aim of this study is to try to replicate these findings using semiqualitative methods. METHODS: Problem-centered interviews were conducted with 78 schizophrenic patients consecutively discharged from inpatient or dayhospital treatment. RESULTS: As in the previous study, patients provided more frequently psychosocial explanations. Biological causes were relatively rarely mentioned--mostly in response to suggestions of the interviewer. In addition, they were rather brief and not very elaborated. By contrast to the previous study, hardly any indications for a multicausal concept could be observed. DISCUSSION: Patients' beliefs are contrasted with the results of psychiatric research on the causes of schizophrenia.

Adult↗
PubMed2001

[Number of hospitalizations according to German "PsychKG" legislation has doubled in 10 years].

AIM: to examine the frequency of involuntary hospitalisation according to PsychKG (german law concerning psychiatric practice) in a comprehensive region with good overall medical/psychiatric services, over the course of a decade. METHOD: All cases of compulsory admission into Psychiatric Clinics within the greater Göttingen area (Central Germany) were evaluated every two years between 1988 and 1998. RESULTS: The number of involuntarily hospitalised patients doubled within the ten years of evaluation although the density of population remained stable and the already good quality out-patient treatment experienced further improvement. However, the total number of in-patients also doubled during this time, so that the proportion between compulsory admission and voluntary hospitalisation remained the same. CONCLUSION: Similar to other regions, the increase in compulsory admissions is considerable. The development towards shorter treatments and an increasing frequency of re-hospitalisation seem to have no significant influence on the courses of disease or on future pathological crises of the patients in question. It is possible that the expected lack of a decreasing rate of compulsory admission is partly caused by behaviour on the part of the physician.

Commitment of Persons with Psychiatric Disorders↗
PubMed2001

[Causal beliefs of schizophrenic patients].

RESEARCH QUESTION: Aim of the study is to investigate whether the preference of schizophrenic patients for psychosocial causal explanations found in a previous study carried out in Hamburg can be observed elsewhere. Further aim of the study was to find out how stable patients' causal attributions are over time. Finally, we were interested to know to what degree patients' beliefs reflect those held by the general public. METHOD: Using an inventory comprising 15 items, we inquired about 105 schizophrenic patient's aetiological ideas at the time of discharge from hospital from inpatient or daycare treatment at 4 psychiatric hospitals in Germany. Follow-ups were carried out 3 months and 6 months later. RESULTS: Psychosocial factors, especially psychosocial stress, were most frequently held responsible for the onset of the illness. The possibility that biological factors might play a role in the causation of schizophrenia was considered more rarely by the patients. There were practically no regional variations as concerns aetiological beliefs. The tendency to endorse psychosocial stress factors was more pronounced among patients as compared with the general public. In total the causal beliefs proved to be quite stable over a time period of 6 months. DISCUSSION: Patients' causal beliefs are compared with findings of psychiatric research, and possible ways to bridge the gap between the two are discussed.

Adult↗
PubMed2001

p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis.

BACKGROUND: Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis. METHODS: Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing. RESULTS: Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease. CONCLUSION: p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.

Adolescent↗
PubMed2001

A prospective study of factors influencing adherence to a continuous neuroleptic treatment program in schizophrenia patients during 2 years.

Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients. There is a lack of prospective studies on factors that predict medication adherence. We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospective study involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two (34.4%) were classified as patient-related dropouts. No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables, except that compliant patients were significantly older. Also, no differences in psychopathology were seen at the beginning of treatment, but compliant patients had a longer duration of illness. Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs. Physicians rated compliant patients from the beginning as more cooperative. These patients also showed significantly higher scores in positive treatment expectations. In a stepwise regression analysis, positive illness concepts, the global assessment of functioning (GAF), and the physicians' view of patients' cooperation predicted 19 percent of the variance. We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem. Future research should focus more on context factors in the search for clinically meaningful explanations of patient dropout from treatment.

Adult↗
PubMed2001

Pancreatic adenocarcinoma cell lines show variable susceptibility to TRAIL-mediated cell death.

BACKGROUND AND AIMS: Programmed cell death via the Fas receptor/Fas Ligand and DR4, DR5/TRAIL plays a major role in tumor escape and elimination mechanisms. It also promises to be an effective therapy alternative for aggressive tumors, as has been recently shown for colon, breast, and lung cancer cells. We attempted to clarify the role of these molecules in aggressivity of pancreatic carcinomas and to identify possible pathways as targets for therapy. METHODS: Five pancreatic cell lines were investigated for the expression of FasL/Fas, DcR3, DR4, DR5/TRAIL, DcR1, DcR2, and other death pathways related molecules such as Bax, bcl-xL, bcl-2, FADD, and caspase-3 by flow cytometry, immunoblotting, and RT/PCR, both semiquantitative and real time (TaqMan). The susceptibility of these cell lines to apoptosis mediated by recombinant TRAIL was investigated. The effect of therapeutic agents (gemcitabine) on their susceptibility to TRAIL induced apoptosis was studied as well. RESULTS: Pancreatic adenocarcinomas expressed high levels of apoptosis-inducing receptors and ligands. They showed differential susceptibility to cell death induced by TRAIL, despite expressing intact receptors and signaling machineries. Treatment with commonly used therapeutic agents did not augment their susceptibility to apoptosis. This could be explained by the fact that they expressed differentially high levels of decoy receptors, as well as molecules known as inhibitors of apoptosis. CONCLUSIONS: The data suggest that pancreatic carcinoma cells have developed different mechanisms to evade the immune system. One is the expression of nonfunctional receptors, decoy receptors, and molecules that block cell death, such as bcl2 and bcl-xL. The second is the expression of apoptosis-inducing ligands, such as TRAIL, that could induce cell death of immune cells. The success in treating malignant tumors by recombinant TRAIL might apply to some but not all pancreatic tumors because of their differential resistance to TRAIL-induced cell death.

Adenocarcinoma↗