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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Adult↗
PubMed2005

Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin.

Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS(2a)). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS(2a) fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg(-1) AlPcS(2a), and 6 h after direct intratumour injection of 50 microg gelonin (PCI) or a similar volume of phosphate-buffered saline (PDT controls), tumour-bearing animals were exposed to red light (150 J cm(-2)). Complete response was observed for more than 100 days in 50% of the PCI tumours but only 10% of the PDT tumours (P<0.01). In tumours examined histologically 4 days after light delivery, the depth of necrosis was 3-4 mm after PDT, but 7 mm after PCI. The deeper effect after PCI demonstrates that the light fluence needed to kill tumour is less than with PDT. We conclude that PCI with gelonin can markedly enhance the effect of PDT on this type of tumour and may have a role clinically as an adjunct to surgery to control localised disease.

Animals↗
PubMed2005

[How well aware of their risk profile are patients with peripheral occlusive arterial disease?].

Today, the majority of physicians no longer consider the well-informed patient to be something of a headache--rather, they welcome him as a partner in the management of his disease. The reason for this is that the more he knows about his illness, the more reliably will he comply with the physician's proposed treatment, the more readily he will be- come aware of side effects, and will thus actively contribute to his recovery. With the aid of easy-to-complete questionnaires, the state of knowledge of POAD patients about their disease was determined. The information thus gained may be considered the basis for an individual physician/patient talk.

Arterial Occlusive Diseases↗
PubMed2005

Structural and oxidation state changes of the photosystem II manganese complex in four transitions of the water oxidation cycle (S0 --> S1, S1 --> S2, S2 --> S3, and S3,4 --> S0) characterized by X-ray absorption spectroscopy at 20 K and room temperature.

Structural and electronic changes (oxidation states) of the Mn(4)Ca complex of photosystem II (PSII) in the water oxidation cycle are of prime interest. For all four transitions between semistable S-states (S(0) --> S(1), S(1) --> S(2), S(2) --> S(3), and S(3),(4) --> S(0)), oxidation state and structural changes of the Mn complex were investigated by X-ray absorption spectroscopy (XAS) not only at 20 K but also at room temperature (RT) where water oxidation is functional. Three distinct experimental approaches were used: (1) illumination-freeze approach (XAS at 20 K), (2) flash-and-rapid-scan approach (RT), and (3) a novel time scan/sampling-XAS method (RT) facilitating particularly direct monitoring of the spectral changes in the S-state cycle. The rate of X-ray photoreduction was quantitatively assessed, and it was thus verified that the Mn ions remained in their initial oxidation state throughout the data collection period (>90%, at 20 K and at RT, for all S-states). Analysis of the complete XANES and EXAFS data sets (20 K and RT data, S(0)-S(3), XANES and EXAFS) obtained by the three approaches leads to the following conclusions. (i) In all S-states, the gross structural and electronic features of the Mn complex are similar at 20 K and room temperature. There are no indications for significant temperature-dependent variations in structure, protonation state, or charge localization. (ii) Mn-centered oxidation likely occurs on each of the three S-state transitions, leading to the S(3) state. (iii) Significant structural changes are coupled to the S(0) --> S(1) and the S(2) --> S(3) transitions which are identified as changes in the Mn-Mn bridging mode. We propose that in the S(2) --> S(3) transition a third Mn-(mu-O)(2)-Mn unit is formed, whereas the S(0) --> S(1) transition involves deprotonation of a mu-hydroxo bridge. In light of these results, the mechanism of accumulation of four oxidation equivalents by the Mn complex and possible implications for formation of the O-O bond are considered.

Freezing↗
PubMed2005

[Organ donation in Switzerland].

Since 1985 Swisstransplant coordinates all allocations for organ transplantations in Switzerland. During these 20 years the number of deceased donors decreased, while the number of living donors increased. In the same period the number of patients on a waiting list for organ transplantation increased significantly, up to more than 1000 at the end of2004. During the year 2004 412 patients were transplanted, 43 (4%) died while waiting on the list. In comparison to other European countries the frequency of organ donation from deceased donors is relatively low in Switzerland, only 13 per million inhabitants. In order to treat the high number of patients needing organ transplantation, additional efforts have to be undertaken in future. The measures include the development of alternative therapies preventing or treating organ failure, the amelioration of legal conditions of organ transplantation with the new law, an increase of resources and knowledge to improve donor evaluation and donor pools in the donor hospitals, a further improvement of the allocation process, the enhancement of information and motivation of the population by the patient organisations, the medical staff, Swisstransplant and eventually public means.

Organ Transplantation↗
PubMed2005

[The role of projectional radiography in the detection of primary malignant and indeterminate bone neoplasms].

PURPOSE: To evaluate the role of projectional radiography in the detection of primary and potentially malignant bone neoplasms. MATERIALS AND METHODS: We retrospectively reviewed the images and medical records of 80 patients (42 male, 38 female; range: 6 to 73 years; mean: 33 years) with pathologically proven primary or indeterminate bone tumors. RESULTS: The most common symptom was local pain (84 %). In 69 of 80 patients (86 %), projectional radiography was the first imaging modality, which correctly identified the malignant character of the bone lesion in 60 of these 69 patients (87 %). In 2 patients, bone neoplasms were overlooked due to diagnostically inadequte image quality. The false-diagnosis rate was not significantly different between board-certified radiologists working in hospitals and radiologists in outpatient facilities (p > 0.05). Bone tumors predominantly affecting adults, such as chondrosarcomas, needed a longer time for the diagnosis than bone tumors mainly found in childhood, such as osteosarcomas. The median age of patients with delayed imaging work-up because of attempted conservative therapy (45 years +/- 20 years) was significant higher than the median age of patients with immediate radiographic work-up (27 years +/- 16 years). CONCLUSION: Projectional radiography is the most common initial imaging method for bone pain and continues to play an important role to reduce the time gap between first onset of symptoms and definitive treatment. In unremitting focal bone pain, bone neoplasms should be taken into consideration not only in children but also in patients beyond adolescence.

Adult↗
PubMed2005

[Thoracic real-time MRI: experience from 2200 examinations in acute and ill-defined thoracic diseases].

PURPOSE: To retrospectively assess the indication for thoracic real-time MRI, demonstrate typical findings, analyze the diagnostic potential in subgroups with suspected pulmonary embolism (PE) and aortic dissection (AD), and describe the influence of real-time MRI on the role of MRI in acute thoracic diseases. MATERIALS AND METHODS: From July 2001 to February 2005, real-time MRI was applied in 2,256 examinations in 1,714 patients. MRI was the primary diagnostic modality for these thoracic diseases as computed tomography has been available only since 2003. Characteristics of the TrueFISP sequence applied were: TR/TE/flip angle 3.1 ms/1.6 ms/59 degrees , respectively. FOV 340 - 360 mm, matrix size 156 to 192 x 256 pixels, slice thickness 3 to 4 mm, slices overlapped by 50 %. Acquisition time was 0.4 to 0.5 s per image. Three hundred and twenty transverse, coronal and sagittal images were acquired in three minutes. No breath holding, and only minimal patient cooperation, was required. Turbo-spin-echo sequences as well as ECG-gated and contrast-enhanced sequences were added depending on the indication. RESULTS: Most common indications were: acute thoracic nonspecified disease (n = 276, 12.24 %), PE (n = 573, 25.4 %), bleeding (n = 154, 6.8 %), AD (n = 222, 9.8 %), topographic information in complex findings (n = 654, 29.0 %). Real-time MRI was the sole MRI technique applied in 180 examinations (8.0 %), ECG-gated real-time MRI was applied in 87 examinations and breath hold was used in 107 examinations. PE was diagnosed in 181 examinations; reference techniques (MRI, computed tomography, single photon emission computed tomography) confirmed 170 of these and detected 19 more cases (sensitivity 90.0 %, specificity 97.1 %). Real-time MRI detected 141 suspected AD and 53 more nonsuspected AD. Of these, 191 were confirmed by other MRI techniques, surgery or clinical course (98.5 %). Real-time MRI coincidentally detected 56 pulmonary tumors, all were confirmed with computed tomography. Thus, especially vascular diseases could be easily assessed with real-time MRI, while computed tomography had advantages in the evaluation of the lung parenchyma. CONCLUSION: Real-time MRI both enables emergency MRI examinations for thoracic diseases in clinical patients in unstable condition and allows an explorative style of working in patients with nondefined acute thoracic diseases.

Acute Disease↗
PubMed2005

Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.

Age of Onset↗
PubMed2005

Evaluation of clinical signs and causes of lower urinary tract disease in European cats.

OBJECTIVES: To investigate the clinical signs and causes of lower urinary tract disease (LUTD) in 77 cats. METHODS: Cats diagnosed with LUTD over a two-year period were included in the study. RESULTS: The study population comprised 67 male and 10 female cats. Uroliths occurred in 17 of the 77 cats (22 per cent), urethral plugs in eight cats (10 per cent) and urinary tract infection in six cats (8 per cent). In 44 cats (57 per cent), no specific cause for the disease was found and they were classified as having idiopathic LUTD. In two of the 77 cats (3 per cent) no definitive diagnosis was established. Pain was less common in cats with uroliths and haematuria was more often seen in cats with urinary tract infection. At presentation, urethral obstruction was diagnosed in 45 of the 77 cats (58 per cent). CLINICAL SIGNIFICANCE: The causes of LUTD found in cats in this study are similar to those that have been previously documented, and idiopathic LUTD is the most frequent diagnosis. However, the rate of urethral obstruction, particularly in cats with idiopathic LUTD, was higher than in other reports. The cause of this difference is unknown.

Animals↗
PubMed2004

Functional role of TRPC proteins in vivo: lessons from TRPC-deficient mouse models.

In order to elucidate the functional role of TRPC genes, in vivo, the targeted inactivation of these genes in mice is an invaluable technique. In this review, we summarize the currently available results on the phenotype of TRPC-deficient mouse lines. The analysis of mice with targeted deletion in three TRPC genes demonstrates that these proteins represent essential constituents of agonist-activated and phospholipase C-dependent Ca2+ entry channels in primary cells. Furthermore, from the deficits observed in these TRPC-deficient mouse lines a striking number of biological functions could already be ascribed to TRPC2, TRPC4, and TRPC6, not only on the cellular level but also for complex organ functions and integrative physiology. Accordingly, TRPC2 proteins are critically involved in pheromone sensing by neurones of the vomeronasal organ and, thereby, in the regulation of sexual and social behavior of mice, TRPC4 proteins are essential determinants of endothelial-dependent regulation of vascular tone, endothelial permeability, and neurotransmitter release from thalamic interneurones, and TRPC6 proteins are supposed to have a fundamental role in the regulation of smooth muscle tone in blood vessels and lung.

Animals↗
PubMed2004

Nitrogen-containing bisphosphonates inhibit cell cycle progression in human melanoma cells.

Cutaneous melanoma is one of the highly malignant human tumours, due to its tendency to generate early metastases and its resistance to classical chemotherapy. We recently demonstrated that pamidronate, a nitrogen-containing bisphosphonate, has an antiproliferative and proapoptotic effect on different melanoma cell lines. In the present study, we compared the in vitro effects of three different bisphosphonates on human melanoma cell lines and we demonstrated that the two nitrogen-containing bisphosphonates pamidronate and zoledronate inhibited the proliferation of melanoma cells and induced apoptosis in a dose- and time-dependent manner. Moreover, cell cycle progression was altered, the two compounds causing accumulation of the cells in the S phase of the cycle. In contrast, the nonaminobisphosphonate clodronate had no effect on melanoma cells. These findings suggest a direct antitumoural effect of bisphosphonates on melanoma cells in vitro and further support the hypothesis of different intracellular mechanisms of action for nitrogen-containing and nonaminobisphosphonates. Our data indicate that nitrogen-containing bisphosphonates may be a useful novel therapeutic class for treatment and/or prevention of melanoma metastases.

Antimetabolites↗
PubMed2004

Impact of diabetes mellitus on long-term outcome after unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy.

AIMS/HYPOTHESIS: We sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy. METHODS: We carried out a prospective cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infarction. All patients underwent coronary angiography and, if appropriate, subsequent revascularisation within 24 hours of admission. The primary endpoint was all-cause mortality during follow-up for up to 60 months. RESULTS: Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention was performed in 53% of diabetic patients and 56% of non-diabetic patients. Coronary artery bypass grafting was done in 21% of diabetic patients and 12% of non-diabetic patients. In-hospital mortality (4.1% vs 1.3%; hazard ratio 3.47; 95% CI: 1.57 to 7.64; p=0.002) and long-term mortality (9.7% vs 4.9%; hazard ratio 2.11; 95% CI: 1.33 to 3.36; p=0.002) were significantly higher in diabetic patients. After adjustment for differences in baseline characteristics, diabetes mellitus was no longer an independent predictor of long-term mortality (hazard ratio 1.43; 95% CI: 0.74 to 2.78; p=0.292). CONCLUSIONS/INTERPRETATION: Diabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infarction have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction.

Aged↗
PubMed2004

Effect of acute brain death on release of atrium and B-type natriuretic peptides in an animal model.

INTRODUCTION: Atrium and B-type natriuretic peptides (ANP and BNP) and big endothelin (ET)-1 are markers for severity of heart failure and may be used in the quality assessment of donor hearts. Elevated cardiac troponins predict early graft failure after heart transplantation. This study evaluated the effects of acute brain death (BD) on the release of ANP, BNP, big ET-1, and cardiac troponins in an animal model. MATERIALS AND METHODS: Pigs were randomized into a BD group (n=5) and a control group (n=5). In the first group, acute BD was induced, and anesthesia was stopped. In the control animals, a sham operation was performed, and anesthesia was continued. Parameters were measured at baseline and for 13 hours postoperatively. RESULTS: After acute BD, there were significant hemodynamic changes. In the control group, the BNP level was higher than in the BD group and decreased over time (P =0.016). There was no significant change in BNP release in the BD group up to 13 hours (P =0.1). ANP release remained stable over time in the control group (P =0.35) but decreased in the BD group (P =0.043). The big ET-1 levels were not different between groups. Cardiac troponin I was elevated in the BD group 5 hours after BD (P< 0.05) but remained under 1.5 mg/L throughout the study. CONCLUSION: Acute BD did not lead to an increase of BNP and ANP levels. Moreover, intact brain function seems to augment the release of natriuretic peptides from the myocardium. Further clinical evaluation of prognostic values of natriuretic peptides for the assessment of donor hearts is necessary. Cardiac troponins are a useful additional tool in the evaluation of donor hearts.

Acute Disease↗
PubMed2004

Noninvasive quantification of brain edema and the space-occupying effect in rat stroke models using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema? METHODS: Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared. RESULTS: Interobserver and intraobserver agreements for MRI measurements were excellent (r>or=0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (r>or=0.95). Corrected lesion volumes correlated with r=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia. CONCLUSIONS: Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.

Animals↗
PubMed2004

Reference values for cardiac troponins I and T in a goal-oriented concept of health: cardiac marker values in a series of outpatients without acute coronary syndromes.

BACKGROUND: Cardiac troponins are part of the new definition of acute myocardial infarction (AMI) by the European Society of Cardiology and the American College of Cardiology (ESC/ACC). In the new guidelines, it was suggested to establish reference values for cardiac troponins to calculate the 0.99 quantile (Q99) as cutoff for AMI diagnosis. PATIENTS AND METHODS: We run a prospective series of troponin measurements in unselected outpatients who had no suspicion of cardiac ischemia. The selection of patients as reference population is based on a "goal-oriented concept of health". One hundred and ninety-five patients agreed that 10-ml additional blood was drawn at the occasion of the venous puncture done routinely in the evaluation of their case. Cardiac troponin I was measured using a point of care (POCT) device (Stratus CS, DadeBehring, TNI-PO). Additionally, heparin-plasma was obtained and immediately deep-frozen to -80 degrees C for later batch measurement of cardiac troponin T (Elecsys 2010, Roche Diagnostics, TnT) and troponin I (Centaur, Bayer, TnI-CL). RESULTS: The Q99 values were 0.14 microg/l for TnI-PO, 0.023 microg/l for TnT and 0.07 microg/l for TnI-CL in patients with creatinine levels below 1.5 mg/dl. These values lay above those obtained from people at good health for reference study purposes. On the level of our cutoffs, CVs were 7.5%, 6.4% and 23.7% for TnI-PO, TnT and TnI-CL, respectively. CONCLUSIONS: Only the TnI-PO and TnT tests fulfilled the imprecision criteria in our study. TnI-PO values between 0.10 and 0.14 microg/l and TnT values between 0.01 and 0.03 microg/l have to be interpreted carefully. Patients presenting with chest pain will be possibly true positives, but patients without chest pain and nondiagnostic ECGs should be subjected to repetitive troponin measurements and further noninvasive investigation and maybe not directly sent to the cardiac catheter laboratory.

Adult↗
PubMed2004

High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and in naturally FCoV-infected cats.

Specified pathogen-free cats were naturally infected with FCoV or experimentally infected with FCoV type I. Seroconversion was determined and the course of infection was monitored by measuring the FCoV loads in faeces, whole blood, plasma and/or monocytes. Tissue samples collected at necropsy were examined for viral load and histopathological changes. Experimentally infected animals started shedding virus as soon as 2 days after infection. They generally displayed the highest viral loads in colon, ileum and mesenteric lymph nodes. Seroconversion occurred 3-4 weeks post infection. Naturally infected cats were positive for FCoV antibodies and monocyte-associated FCoV viraemia prior to death. At necropsy, most animals tested positive for viral shedding and FCoV RNA was found in spleen, mesenteric lymph nodes and bone marrow. Both experimentally and naturally infected cats remained clinically healthy. Pathological findings were restricted to generalized lymphatic hyperplasia. These findings demonstrate the presence of systemic FCoV infection with high viral loads in the absence of clinical and pathological signs.

Animals↗