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Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 127 records · Page 7Linked to original sources

Mildly oxidized low density lipoprotein rapidly stimulates via activation of the lysophosphatidic acid receptor Src family and Syk tyrosine kinases and Ca2+ influx in human platelets.

In contrast to native low density lipoprotein (LDL), mildly oxidized LDL (mox-LDL) induced platelet shape change and stimulated during shape change the tyrosine phosphorylation of specific proteins including Syk; the translocation of Src, Fyn, and Syk to the cytoskeleton; and the increase of cytosolic Ca(2+) due to mainly Ca(2+) entry. The stimulation of these early signal pathways by mox-LDL was inhibited by desensitization of the lysophosphatidic acid (LPA) receptor and specific LPA receptor antagonists, was independent of the alpha(IIb)beta(3)-integrin, and was mimicked by LPA. Stimulation of tyrosine phosphorylation and Syk activation were independent of the increase of cytosolic Ca(2+) and were suppressed by genistein and two specific inhibitors of the Src family tyrosine kinases, PP1 and PD173956. In contrast to PP1 and PD 173956, genistein prevented shape change by mox-LDL. The results indicate that mox-LDL, through activation of the LPA receptor, stimulates two separate early signal pathways, (a) Src family and Syk tyrosine kinases, and (b) Ca(2+) entry. The activation of these early signaling pathways by mox-LDL probably plays a role in platelet responses subsequent to shape change. The inhibition of mox-LDL-induced platelet activation by LPA receptor antagonists or dietary isoflavonoids such as genistein could have implications in the prevention and therapy of cardiovascular diseases.

Blood Platelets↗

Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation.

The crystal structure of a constitutively active multiple site mutant of plasminogen activator inhibitor 1 (PAI-1) was determined and refined at a resolution of 2.7 A. The present structure comprises a dimer of two crystallographically independent PAI-1 molecules that pack by association of the residues P6 to P3 of the reactive centre loop of one molecule (A) with the edge of the main beta-sheet A of the other molecule (B).Thus, the reactive centre loop is ordered for molecule A by crystal packing forces, while for molecule B it is unconstrained by crystal packing contacts and is disordered. The overall structure of active PAI-1 is similar to the structures of other active inhibitory serpins exhibiting as the major secondary structural feature a five-stranded beta-sheet A and an intact proteinase-binding loop protruding from the one end of the elongated molecule. No preinsertion of the reactive centre loop is observed in this structure.A comparison of the present structure with the previously determined crystal structures of PAI-1 in its alternative conformations reveals that, upon cleavage of an intact form of PAI-1 or formation of latent PAI-1, the well-characterised rearrangements of the serpin secondary structural elements are accompanied by dramatic and partly unexpected conformational changes of helical and loop structures proximal to beta-sheet A. The present structure explains the stabilising effects of the mutated residues, reveals the structural cause for the observed spectroscopic differences between active and latent PAI-1, and provides new insights into possible mechanisms of stabilisation by its natural binding partner, vitronectin.

Amino Acid Sequence↗

Cerebellar vermis area in schizophrenic patients - a post-mortem study.

Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.

Adolescent↗

HPV type 16 protein E7 HLA-A2 binding peptides are immunogenic but not processed and presented.

Human papillomaviruses (HPV) have been implicated in the etiology of cervical malignancies and a high percentage of cervical carcinoma cells express HPV-16 E6 and E7 oncoproteins. These proteins are attractive targets for cytolytic T lymphocyte (CTL) mediated immunotherapy. We screened peptides derived from the HPV-16 E7 protein for binding to HLA-A2 and tested their potential to induce specific CTL responses in chimeric HLA-A2/H2-Kb transgenic mice. From eight potential binding peptides four displayed binding and were tested for immunogenicity. CTL activity was tested using target cells pulsed with peptide or expressing E7 protein. While there was no CTL induction observed with the peptides 7-15, 66-74 and 82-90, CTL from mice immunized with 86-93 lysed targets presenting the peptide in the context of the HLA-A2/H2-Kb molecule or wild-type HLA-A2. In contrast, 86-93 induced CTL showed no cytolytic activity against cells expressing the protein E7 and vaccination with the E7 protein did not lead to cytotoxicity against targets pulsed with the 86-93 peptide. Therefore the peptide 86-93, which binds to HLA-A2, is able to induce CTL responses in context of HLA-A2, but the peptide appears not to be processed or presented by HPV type 16 infected cells.

Animals↗

Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen.

Continuous intravenous infusion of norepinephrine norepinephrine (NE, 0.1 mg/kg/h) induced hypertrophy of the left ventricle (LV), but not of the right ventricle (RV) in rats, although RV systolic pressure (RVSP) was much more elevated than LVSP. After NE infusion, there was a time-dependent (20 min to 72 h) expression in the mRNA of interleukin (IL)-6 and IL-1 beta. The expression of IL-6 increased markedly and reached the maximum after 4 h with an 80-fold elevation. In the RV, the expression increased only 20-fold. The mRNA of IL-1 beta increased significantly after NE stimulation only in the LV and reached the maximum after 12 h with a 12-fold elevation. After 12 h of NE infusion, colligin mRNA was elevated for the first time with further progression until 72 h. The six-fold abundance of colligin mRNA seen after 72 h was significantly higher in the LV than in the RV. A similar increase was observed on the protein level (Western blotting). The expression of collagen I and III increased significantly after 24 h only in the LV. After 72 h, the mRNA expression of collagen I was increased 16-fold and that of collagen III 10-fold. This expression was significantly higher than that in the RV. Also the elevation in atrial natriuretic peptide (ANP) mRNA started earlier and was more pronounced in the LV than in the RV. The alpha- and beta-adrenergic receptor blocker carvedilol normalized all functional parameters after 6 h and 72 h and prevented the development of LV hypertrophy that occurred after 72 h. The NE-induced increased expression of the mRNAs studied was either prevented (IL-6, IL-1 beta ) or attenuated (colligin, collagen I and III, ANP) by combined alpha- and beta-receptor blockade. The elevation of afterload which was associated with the NE effect was normalized by the calcium-channel blocker nisoldipin, but NE-induced LV hypertrophy and the increase in ANP and collagen mRNA were not affected.

Adrenergic Antagonists↗

[Time course of neuromuscular blockade after rocuronium. A comparison between women and men].

BACKGROUND: We studied 40 patients (20 female and 20 male) undergoing elective surgery under general anaesthesia to evaluate the effect of gender on the pharmacodynamics of rocuronium. METHODS: Using electromyography (EMG) we determined the maximal neuromuscular block and time course of action of 0.45 mg/kg rocuronium (1.5 x ED95). RESULTS: Age and body mass index were comparable between females and males (38 (+/- 8) vs. 37 (+/- 10) years and 24.2 (+/- 2.9) vs. 25.2 (+/- 1.7) kg/m2. However, significant differences in weight and height were found between females and males (65.7 +/- 9.3 kg vs. 77.5 +/- 5.5 kg; p < 0.01 and 178 +/- 6.8 cm vs. 164 +/- 6.7 cm; p < 0.01). Onset time was shorter in females (168 +/- 65 s vs. 211 +/- 56 s; p < 0.05). Maximal neuromuscular blockade after 0.45 mg/kg rocuronium was 94 (+/- 3) % in females and 89 (+/- 6) % in males; p < 0.01. Clinical duration was increased in females (23 +/- 5 min vs. 17 +/- 5 min; p < 0.05), while the recovery index was comparable between both groups (9 +/- 4 min in females and 9 +/- 3 min in males; n.s.). CONCLUSION: Compared to men neuromuscular blockade after 0.45 mg/kg rocuronium was more pronounced in women. The onset time was shortened and the clinical duration increased in female patients.

Adult↗

[Mammography].

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Breast Diseases↗

[Ventricular septal aneurysm in a patient with Marfan syndrome].

This is the first description of a patient with Marfan syndrome and an aneurysm of the ventricular septum. Apart from a borderline dilatation of the ascending aorta, there were no cardiovascular manifestations of Marfan syndrome. A transesophageal echocardiographic examination showed a large aneurysm of the ventricular septum. To prevent the imminent rupture and the acute occurrence of a significant left-to-right-shunt on the ventricular level, as well as increasing irritation of tricuspid valve, an elective operation was performed. Besides the routine cardiological diagnostics, the search for intracardial defects is also necessary in patients with Marfan syndrome.

Adult↗

Impersonation of a ruptured thoracic aneurysm by a transdiaphragmatic pancreatic cyst.

Pancreatic cysts can, in rare cases, expand into the posterior mediastinum and may require surgical resection. We present the case of a patient with a thoracic aneurysm, in whom the mediastinal involvement of a chronic pancreatic cyst masqueraded as a ruptured aneurysm. Surgery was undertaken: first, the initial resection and drainage of the thoracic portion of the pseudocyst, and second, a thorough cleansing of the entire cyst through median laparotomy 15 days later.

Aged↗

Surgical treatment of a chest-wall penetrating left ventricular pseudoaneurysm.

This report describes the treatment of a patient who developed a chest-wall penetrating pseudoaneurysm 3 years after coronary bypass grafting and after the resection of a lateral wall left ventricular aneurysm twice. The patient presented with a pulsatile tumor in the left submammilar region. Surgery was done in deep hypothermia, with femoro-femoral cannulation and via a left anterolateral thoracotomy. The perioperative course was uneventful and the patient is still well 5 years after surgery.

Aged↗

Reinforcing the conventional sternal closure.

Sternal infection is a devastating complication of heart surgery. It may be the result of unstable osteosynthesis, caused by the sternal wires cutting into the cortical layers, which results in tension loss and gap formation. We describe a technique that prevents the cerclages from cutting into the sternal plates and covers the sternum with a well-capillarized barrier of major pectoralis muscle.

Aged↗

The biocompound method in coronary artery bypass operations: surgical technique and 3-year patency.

BACKGROUND: Complete arterial revascularization may be unsafe in patients with a high operative risk. In patients with varicose ectatic veins, the biocompound technique, which uses unsuitable autologous veins, enables the surgeon to influence the bypass graft wall stress levels and diameter. This report summarizes the 3-year patency of 53 patients, the survival rate of 200 patients, and operative technical considerations. METHODS: Biocompound grafts were used for aortocoronary bypass in 200 patients who were considered inappropriate subjects for complete arterial revascularization and who had unsuitable saphenous veins. RESULTS: The mortality rate (30 days) of 200 patients was 3.5%. The 3-year survival rate was 88.5%. The patency rate of the left internal thoracic artery (LITA) after 3 years was 97.3%, of the native vein was 68.7%, and of the biocompound graft was 68.3%. The LITA showed a superior patency rate (p = < 0.05). CONCLUSIONS: The LITA is the first choice in coronary bypass operation. The biocompound technique is a reliable method to achieve complete revascularization in patients with a lack of suitable saphenous veins.

Aged↗

Hirudin as anticoagulant for cardiopulmonary bypass: importance of preoperative renal function.

BACKGROUND: Recombinant hirudin is an alternative anticoagulant for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II. Although there is no neutralizing agent for recombinant hirudin, its fast renal elimination enables quick cessation of bleeding after cardiopulmonary bypass. The aim of the study was to compare anticoagulant effects of recombinant hirudin in regards to renal function in patients with heparin-induced thrombocytopenia type II. METHODS: Twenty-one patients (mean age, 65 years, and range, 35 to 82 years) underwent different complex cardiovascular procedures using recombinant hirudin as the anticoagulant for cardiopulmonary bypass. Postoperative blood loss, transfusion requirements, and hemostatic variables were compared between patients with a creatinine level lower than 1.5 mg/dL (group 1, normal renal function; n = 17 patients) and those with a creatinine level greater than 1.5 mg/dL (group 2, impaired renal function; n = 4 patients). RESULTS: The patients in group 1 showed no increased tendency toward postoperative bleeding. In contrast, all 4 patients in group 2 required reexploration for increased postoperative bleeding. They had higher activated partial thromboplastin times and transfusion requirements postoperatively. CONCLUSIONS: If recombinant hirudin is used as the anticoagulant for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and impaired renal function, the risk of postoperative bleeding is increased.

Adult↗

Flexible bronchoscopy: a safe method for metal stent implantation in bronchial disease.

BACKGROUND: Endoscopic bronchoplastic procedures, such as metal stent implantation, are for safety reasons and mainly performed using rigid bronchoscopy. Major complications, such as bleeding and accidental airway occlusion, are thought to be better managed with the rigid device. An increasing number of pneumologists, however, use the flexible fiberscope for endobronchial stenting. METHODS: Sixty-five stent implantations were performed in 51 patients with flexible fiberoptic bronchoscopy. We implanted 27 Tantalum Strecker stents (Boston Scientific Co, Watertown, MA), 20 Nitinol Accuflex stents (Boston Scientific Co) and 18 Wallstents (Schneider, Zurich, Switzerland). Underlying conditions were malignant disease in 84% and benign bronchial collapse in 16%. Sites of implantation were the trachea (45%), the main bronchi (35%), and other locations (20%). In 47 cases the patients received intravenous sedation combined with high frequency jet ventilation, and in 18 cases the patients were treated with topical anesthesia alone. RESULTS: Mean examination time was 58.3 (standard deviation 29.1) minutes. Eighty percent of patients experienced immediate clinical improvement in respiratory symptoms. Spirometric parameters (forced expiratory volume in one second, peak expiratory flow rate, forced vital capacity) increased. Complications included hypertension (17%), hypotension (12%), hypoxia (5%), bronchospasm (4%), initial displacement of the prosthesis (11%), and diameter mismatch between stent and bronchus (5%). All complications were managed safely. Relevant bleeding or asphyxia during the procedure has not been observed. Late stent migration was observed in 12% of cases. There were 3 fatalities within 30 days of stent placement which, however, were not attributed to the implantation technique. CONCLUSIONS: Flexible fiberoptic bronchoscopy is a safe and suitable method to perform endobronchial metal stent implantation. Complications were rare and not serious. Initial misplacement of the prosthesis occurred in some cases and necessitated removal and replacement within the same procedure.

Adult↗

Space- and time-resolved Brillouin light scattering from nonlinear spin-wave packets

We have constructed a new Brillouin light scattering apparatus, based on the Sandercock multipass tandem interferometer design, for space- and time-resolved investigations of nonlinear wave packets in thin films. We have applied the method to studies of nonlinear spin-wave pulse propagation in yttrium iron garnet (YIG) films. Spatial resolution is achieved by scanning the laser spot across the YIG film surface, and temporal resolution is obtained by measuring the elapsed time between the launch of spin-wave pulses by an applied microwave pulse and the arrival of the respective inelastically scattered photons at the detector. We report the observation of nonlinear self-focusing of wave beams and pulses in one and two dimensions, the formation of one-dimensional envelope solitons, and of strongly localized, two-dimensional wave packets, 'spin-wave bullets', analogous to 'light bullets' predicted in nonlinear optics. By generating two counter-propagating wave pulses, pulse collision experiments were performed. We show that quasi-one-dimensional envelope solitons formed in narrow film stripes ('waveguides') retain their shapes after collision, while two-dimensional spin-wave packets formed in wide YIG films are destroyed in collision.

Journal Article↗

Maintenance therapies for classic and other forms of bipolar disorder.

The progressive, episodic and chronic nature of bipolar disorder dictates the need for lifelong pharmacological maintenance treatment in the majority of patients. Prophylaxis should be considered after a single episode of severe mania or after more than one episode of hypomania in bipolar II disorder, although some clinicians now consider an episode of either sufficient to warrant maintenance therapy. Lithium is efficacious as maintenance therapy, but is not as highly effective as early studies initially suggested (abrupt discontinuation of lithium probably increased placebo relapse figures). Rates of premature discontinuation of lithium are high. Divalproex sodium is used frequently in the USA and Canada for long-term treatment for bipolar disorder but an insufficient number of controlled trials have been published to assess adequately its role. Carbamazepine is also employed in maintenance treatment. Randomized studies indicate it is superior to placebo but somewhat less effective than lithium. Augmentation of any of these drugs with another mood stabilizer, an antipsychotic, or electroconvulsive therapy appears to be effective, although there are few controlled studies. Design issues that need consideration in order to achieve meaningful data are discussed. A severe manifestation of bipolar disorder is rapid cycling. It is often induced by antidepressants, although this association frequently goes unrecognized. Patients with a rapid cycling course of illness are difficult to treat effectively. Although rapid cycling is often associated with poor response to lithium, there have been no randomized, controlled treatment studies. Based on open studies and expert panel recommendations, the International Exchange on Bipolar Disorder (IEBD) recommended initial treatment with divalproex sodium, with subsequent addition of other mood stabilizers, antipsychotics or thyroid supplementation as necessary. Combination treatments are frequently required for optimal response in these patients.

Antidepressive Agents↗