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Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 127 records · Page 7Linked to original sources

Changes in myocardial perfusion after catheter-based percutaneous laser revascularisation.

This study investigated the effect of percutaneous laser revascularisation (PMR) on regional myocardial blood flow. PMR is a new therapeutic modality for patients suffering from angina pectoris due to coronary artery disease (CAD) that is not amenable to revascularisation. Initial clinical studies discovered reduced angina pectoris and increased exercise capacity after PMR. There are no previous clinical studies reporting the impact of PMR on perfusion. Thirty-six patients with end-stage CAD underwent thallium-201 single-photon emission tomography studies on four different occasions: immediately before PMR and 3, 6 and 12 months following PMR. Each study consisted of pharmacological stress and rest scintigraphy. Semiquantitative evaluation was performed by use of 14 standardised wall segments which were classified (a) according to the localisation of the PMR target region into treated segments, segments adjacent to the treated area and non-treated segments and (b) according to the pre-therapeutic local perfusion into four groups: no (0), slight (I), moderate (II) or severe (III) perfusion deficit. At stress in treated segments of groups II and III local scintigraphic count densities increased from 60.1% and 34.7% at baseline to 65.3% and 48.3% after 12 months (P<0.05) while they decreased in segments of group 0 from 94.2% to 85.7% (P<0.05). In rest studies no changes occurred. Thus, the local rest-stress differences within the target areas become smaller after PMR. In the PMR target area but not in the nontreated area an improvement in regional myocardial flow reserve occurs in wall segments with initially severely or moderately reduced stress perfusion. This effect is consistent with the clinical improvement after PMR.

Aged↗

[Percutaneous reconstruction of a pelvic vascular occlusion using the "kissing-balloon" technique].

UNLABELLED: A 43-year-old patient was admitted for severe claudication in his right leg, doppler ultrasound and angiography revealed an occluded right common iliac artery. Using the cross-over-approach from the contralateral side, it was possible to navigate a guide wire through the occlusion, and after passage with an excimer laser an ipsilateral retrograde puncture with placement of a sheath was performed. In order to protect the the aortoiliac bifurcation, a primary stent implantation of the occluded side was carried out using the kissing balloon technique. Afterwards three stents were placed. Subsequently the patient completely improved; treadmill exercise test and duplex sonography showed good results. CONCLUSION: Using the kissing balloon technique, laser-assisted recanalisation of iliac artery occlusions even involving the aortoiliac bifurcation compare favorable to other more invasive treatments. A surgical procedure can thus be avoided.

Adult↗

[Intravenous long-term thrombolysis of an occluded aortocoronary venous bypass graft].

A 41-year-old man presented with progressive unstable angina pectoris during the last three hours. At admission the electrocardiogram and cardiac specific enzymes showed no signs of ischemia. During the next 24 hours the electrocardiogram and cardiac enzymes developed signs of a non-Q-wave anterolateral infarction. The patient had known coronary artery disease and underwent aortocoronary bypass surgery seven years ago. Coronary angiography after admission revealed a chronically occluded vein graft to the right coronary artery (RCA) and a subtotal occlusion of the vein graft to the left anterior descending artery (LAD) with a TIMI flow 0-I. Because of unfavorable results of mechanical revascularization of occluded bypass grafts and high risk of catheter dislocation and bleeding complications of intracoronary local thrombolysis, the patient subsequently received intravenous long-term thrombolysis for 24 hours. After successful lysis of the thrombus the bypass graft to the LAD showed two severe stenoses but blood flow has returned to normal. Three days later percutaneous transluminal coronary angioplasty (PTCA) and stent implantation were carried out with a good primary angiographic result. After 6 months the patient was still asymptomatic and a treadmill exercise test showed no signs of ischemia.

Adult↗

[Mediastinal space-occupying lesion as a rare cause of atrial arrhythmia].

HISTORY AND CLINICAL FINDINGS: A 61 year old man presented with newly developed tachyarrhythmia. Echocardiographically a tumour of unclear origin in the left atrium was diagnosed. INVESTIGATIONS: The heart rate in the ECG was arrhythmic at 146/min; intermittently sinus rhythm was established. Transoesophageal echocardiography revealed a 90 x 50 mm tumour with sharp borders displacing both atria. The chest x-ray showed a mediastinal rounded mass in the dorsal part overlapping the right mediastinal border. Computer tomography was unable to discriminate the atrial wall from the tumour masses; hence the difference between an (intra-)cardiac tumour (i.e. myxoma) and a tumour of extracardiac (mediastinal) origin could not be established. Additional magnetic resonance tomography led to the most probable diagnosis of a bronchogenic cyst, which spread ventrally up to the ascending aorta and dorsally to the paravertebral region, thus displacing and shrinking the left pulmonary artery and the left atrium. THERAPY: For certain exclusion of malignancy and because of displacement of other thoracic structures the patient was operated on this mediastinal mass by anterolateral thoracotomy. Histologically a dysontogenetic, benign cyst with an inner layer of mesothel and nerval as well as vascular structures in the capsule was diagnosed. Since the operation the patient has persistent sinus rhythm without symptoms of relevant rhythm disorders. An overview of different kinds of intrathoracical cysts is given.

Atrial Fibrillation↗

[Myocardial laser revascularization in therapy-refractory angina pectoris].

In patients with coronary artery disease and intractable angina, who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment. Several recently published, randomized trials have consistently shown improvement of clinical symptoms and increased exercise capacity after TMR compared to medical therapy. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality. Therefore, catheter-based systems have been developed, which allow creation of laser channels in the myocardium from within the left ventricular cavity. These systems for "percutaneous myocardial revascularization" (PMR) use laser energy generated by Holmium: YAG lasers, which can be transmitted to the myocardium via flexible optical fibers. PMR leads to significant improvement of clinical symptoms and increased exercise capacity similar to TMR. The CCS classification is improved about 1.5 classes, independent of the PMR system used. However, evidence of improved perfusion after PMR is still lacking. The pathophysiologic mechanisms of myocardial laser revascularization are still poorly understood. Experimental studies indicate myocardial neoangiogenesis and myocardial denervation after TMR; however, clinical studies have not yet found evidence of improved myocardial perfusion after myocardial laser revascularization.

Angina Pectoris↗

[Late diagnosis of Curschmann-Steinert myotonic dystrophy in a female patient with dilated cardiomyopathy and in her son].

A 41 year old woman presented with dyspnoea at rest and swollen legs in the emergency room of our centre. She reported a history of slowly progressing dyspnoea and oedema in the legs. Physical examination showed signs of biventricular congestive heart failure and dysmorphia of the face. Routine laboratory examination revealed elevated CK levels without significant elevations of the CK-MB isoform. ECG showed complete left bundle branch block and first degree atrioventricular block. Echocardiography and angiography showed markedly reduced left ventricular systolic function, the ejection fraction was 25%. Coronary angiography excluded CAD and there was no evidence for congenital or valvular heart disease. The patient also reported a history of a serious complication during emergency general anaesthesia and cataracts of both eyes. Because of the clinical and chemical findings, the history of cataracts and complications during general anaesthesia, a systemic congenital disease of the muscular tissue was suspected. Molecular studies revealed a trinucleotide amplification at the myotonic dystrophy locus 19q 13.3, so the diagnosis myotonic dystrophy Curschmann-Steinert was established. The sixteen year old son of the patient suffered from an at this time unknown disease with retardation, muscular weakness and myotonia of the face. The diagnosis myotonic dystrophy was evident because of the clinical signs and the family history.

Adolescent↗

The revival of surgical treatment for isolated proximal high grade LAD lesions by minimally invasive coronary artery bypass grafting.

BACKGROUND: Percutaneous coronary angioplasty (PTCA) and stent implantation have become the first-line intervention for patients with isolated proximal LAD-lesions. Minimally invasive direct coronary artery bypass surgery (MIDCAB) has recently been developed to reduce surgical invasiveness for single LAD revascularization. This study focus on the question whether MIDCAB could be an alternative treatment for isolated proximal LAD lesions. METHODS: Starting in 1996, MIDCAB was performed in 618 patients. Angiography was performed before discharge and repeated after 6 months at follow-up examination. In an ongoing randomized trial 150 patients with an indication for treatment of a LAD lesion have been included to compare the mid-term outcome after PTCA (n=79) vs. MIDCAB (n=71). RESULTS: In 618 MIDCAB procedures 30-day mortality was 0.6%, perioperative myocardial infarction rate was 1.6%. The conversion rate to sternotomy was 3.4%. The learning curve was demonstrated by a patency rate of 96.0% in 1997, 98.0% in 1998 and 99.1% in 1999, respectively. At 6 months patency rate was 94.4% in 1997 and 97.0% in 1998. The rate of severe stenosis >75% dropped from 5.4% in 1997 to 3.4% in 1998. The over all rate of reinterventions was 5.6%. The preliminary result of the randomized trial revealed a difference in the number of perioperative adverse events, 11.4% in the MIDCAB group vs. 6.3% in the PTCA group (P<0.05). At 6 months follow-up 88. 7% of the MIDCAB patients were free from angina vs. 58.2% of the PTCA patients (P<0.02). Restenosis and a positive stress test was diagnosed in 27.9% of the PTCA patients vs. 8.4% of the MIDCAB patients (P<0.02). Reintervention was necessary in 27.9% of the patients after PTCA vs. 8.4% of the patients after MIDCAB. CONCLUSION: MIDCAB is a safe and effective but technically demanding procedure. Perioperative adverse events may be expected, but early as well as mid-term patency rate are good. When compared to PTCA, the freedom from angina and the need for additional revascularization procedures after 6 months is statistically better for patients having MIDCAB surgery. Thus, MIDCAB is considered a valuable alternative for isolated proximal high grade LAD lesions.

Adult↗

Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes.

The use of tumor antigen loaded dendritic cells (DC) is one of the most promising approaches to induce a tumor specific immune response in vivo. Several strategies have been designed to load DC with tumor antigens. In this study, we investigated the delivery of in vitro transcribed RNA and plasmid DNA into monocyte-derived, ie non-proliferating human DC, using several nonviral transfection methods including electroporation and lipofection. Green fluorescent protein (GFP) was used as a reporter gene and influenza matrix protein 1 (M1) as a model antigen for HLA class I restricted antigen presentation. Using electroporation in combination with DNA or with RNA, up to 11% of DC were GFP-positive. Using liposomes as a vehicle for DNA transport up to 10% of the DC were GFP-positive. A significant increase in transfection efficacy, of up to 20%, was observed when GFP RNA was used in combination with liposomes. Importantly, the RNA transfected DC retained their typical morphological and immunophenotypical characteristics. In addition, DC transfected with M1 RNA were able to stimulate autologous peripheral M1-specific memory cytotoxic T lymphocytes (CTL), as well as M1-specific CTL clones. Furthermore, comparison of DNA-transfected DC with RNA-transfected DC revealed the latter to be far better stimulators of antigen-specific T cells. This RNA transfection technique consequently represents a very promising tool for future immunotherapy strategies.

Antigens, Viral↗

Prevention of latex allergy by selection of low-allergen gloves.

BACKGROUND: In recent years the prevalence of type I allergy to latex has continuously increased, in particular among healthcare workers, to about 10%. While most forms of type I allergy caused by other environmental allergens can be treated by pharmacotherapy or specific immunotherapy, minimizing exposure to latex proteins may represent an effective preventive measure for latex allergy. OBJECTIVE: To investigate whether it is possible to select by in vitro and in vivo testing low-allergen latex gloves for prevention of latex allergy. METHODS: We obtained separate extracts by standard aqueous extraction from the inner and outer surfaces of 15 different commonly used (10 examination, five surgical) glove brands. The extracts were analysed by quantitative (bicinchoninic protein assay, immunoglobulin [Ig] E-ELISA, ELISA competition) and qualitative (SDS-PAGE, silver staining, IgE immunoblotting) methods for their protein and allergen contents. In addition, the glove extracts were analysed for their capacity to induce basophil histamine release and immediate skin reactions. RESULTS: Extracts from different glove brands contained cross-reactive IgE epitopes. However, IgE binding studies, basophil histamine release and skin testing showed that different glove brands and their inner and outer surfaces contained widely varying protein and allergen contents. While the determination of total protein contents was not sufficient to identify low-allergen gloves, IgE measurements, basophil histamine release and skin testing were in good agreement and allowed to select low-allergen products. CONCLUSION: We suggest the use of low-allergen latex products identified by IgE binding, basophil histamine release assays and skin testing as a feasible preventive measure for latex allergy.

Adolescent↗

Formation and kinetics of MHC class I-ovalbumin peptide complexes on immature and mature murine dendritic cells.

Dendritic cells (DC) are professional antigen-presenting cells that are able to induce primary T cell responses. Therefore, several strategies employ peptide-pulsed DC in tumor immunotherapy. For efficient antigen presentation and induction of an immune response by DC the number and stability of MHC I-peptide complexes is crucial. We studied this issue by using the antibody 25-D1.16 that specifically detects OVA peptide SIINFEKL in conjunction with H-2 Kb molecules, and determined its kinetics on mature and immature bone marrow-derived murine DC. Optimal peptide loading was reached after 8-16 h at 50 microM peptide pulse, and was comparable in serum-free versus serum-containing medium. Stimulation of DC with LPS or Poly I:C, and to a lesser extent TNF-alpha, upregulated the total number of surface MHC I molecules and thus improved peptide loading. Pulse-chase experiments revealed a constant half-life of peptide/Kb complexes independent of preceding DC stimulation or their maturation stage. The duration of peptide/Kb complex expression on mature DC, however, could be extended from 24 h to 72 h when the cultures were pretreated with LPS or Poly I:C, but not TNF-alpha. These data might have important implications for the clinical application of peptide-pulsed DC in tumor immunotherapy.

Aging↗

Mutual boosting effects of sensitization with timothy grass pollen and latex glove extract on IgE antibody responses in a mouse model.

Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from pollen allergies may have pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed pollen extracts from timothy grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after pollen sensitization and vice versa. Moreover, mice immunized with timothy grass pollen extract alone - without subsequent latex immunization - displayed IgE reactivity to latex. Cross-reactive antibodies were directed against pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients.

Allergens↗

[Secondary splenic rupture after thrombolysis for acute myocardial infarction]

Secondary splenic rupture after thrombolysis for acute myocardial infarction. HISTORY AND ADMISSION FINDINGS: A 67-year-old male patient was admitted with acute chest pain and signs of an acute anterior myocardial infarction in the ECG. The usual contraindications were excluded and after a systemic lysis with rt-PA the ECG-alterations as well as the symptoms of angina resolved completely. 2 hours later the patient developed an acute abdomen with a severe circulatory shock. INVESTIGATIONS: On ultrasound and CT a massive intraabdominal bleeding was found. TREATMENT AND COURSE: Emergency laparotomy revealed a splenic rupture. Retrospectively, 6 weeks before admission, the patient had fallen from a ladder to his left side. This is a rare case of a secondary splenic rupture during thrombolysis for acute myocardial infarction. 2 weeks later the patient developed rein-farction with angiographically shown two vessel disease. After angioplasty of the ramus interventricularis anterior (RIVA) he was stable. CONCLUSIONS: Intravenous thrombolysis in case of acute myocardial infarction is the method of choice. In the past a great number of patients were excluded from thrombolysis because of an extensive interpretation of contraindications. The aim to reach an alteration in this use may not risk health of patients by insufficient history.

Journal Article↗

Mature dendritic cells infected with herpes simplex virus type 1 exhibit inhibited T-cell stimulatory capacity.

Mature dendritic cells (DC) are the most potent antigen-presenting cells within the entire immune system. Interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. Several members of the Herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. In this study we investigated the infection of mature DC with herpes simplex virus type 1 (HSV-1) and the way in which infection alters the phenotype and function of mature DC. Interestingly, the T-cell-stimulatory capacity of these DC was strongly impaired. Furthermore, we demonstrated that HSV-1 leads to the specific degradation of CD83, a cell surface molecule which is specifically upregulated during DC maturation. These data indicate that HSV-1 has developed yet another novel mechanism to escape immune responses.

Antigens, CD↗

[Percutaneous myocardial laser revascularization (PMR), a new therapeutic procedure for patients with refractory angina pectoris].

In patients with severe angina pectoris due to coronary artery disease, who are not candidates for either percutaneous coronary angioplasty or coronary artery bypass surgery, transmyocardial laser revascularization (TMR) often leads to improvement of clinical symptoms and increased exercise capacity. One drawback of TMR is the need for surgical thoracotomy in order to gain access to the epicardial surface of the heart. Therefore, a catheter-based system has been developed, which allows creation of laser channels into the myocardium from the left ventricular cavity. Between January 1997 and November 1999, this "percutaneous myocardial laser-revascularization" (PMR) was performed in 85 patients at the Herzzentrum Leipzig. In 43 patients, only one region of the heart (anterior, lateral, inferior or septal) was treated with PMR; in 42 patients two or three regions were treated in one session. 12.3 +/- 4.3 (range 4-22) channels/region were created into the myocardium. Six months after PMR, the majority of patients reported significant improvement of clinical symptoms (CCS class at baseline: 3.3 +/- 0.4; after 6 months: 1.6 +/- 0.9) (p < 0.001) and an increased exercise capacity (baseline: 349 +/- 138 s; after 6 months: 470 +/- 193 s) (p < 0.05); however, thallium scintigraphy failed to show increased perfusion in the PMR treated regions. PMR seems to be a safe and feasible new therapeutic option for patients with refractory angina pectoris due to end-stage coronary artery disease. The first results indicate improvement of clinical symptoms and increased exercise capacity; evidence of increased perfusion in the laser-treated regions is still lacking.

Adult↗

Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma.

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1-specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL-tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

Adult↗