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Biomedical subjects

J Richter

Publications and source records attributed to J Richter.

At least 55 records · Page 3Linked to original sources

Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent.

To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.

Animals↗

Different preservation of myocardial capillary endothelial cells and cardiomyocytes during and after cardioplegic ischemia (25 degrees C) of canine hearts.

Complete resumption of cardiac function after cardioplegic arrest presupposes a well-preserved myocardial ultrastructure during and after ischemia. Therefore, we determined ischemia-induced ultrastructural alterations in the myocardium during and after reversible cardioplegic ischemia using stereological methods. Cardiac arrest was induced with St. Thomas' Hospital- or Custodiol (HTK) solution. Reperfusion with Tyrode's solution followed after reversible cardioplegic ischemia in situ. Samples were taken 1) from beating hearts, 2) from cardioplegically arrested hearts immediately after the end of coronary perfusion, 3) from ischemic hearts incubated in the cardioplegic solution at 25 degrees C, and 4) from reperfused beating hearts after ischemia in situ at 22 degrees C. Cellular swelling was determined as the barrier thickness of capillary endothelium and as the sum of cardiomyocyte volume fractions of free sarcoplasm and mitochondria. In St. Thomas'-arrested hearts, intraischemic volume increase was significantly more pronounced in endothelial cells than in cardiomyocytes. Reperfusion at the intraischemic practical limit of resuscitability (ATP levels of 4 micromol/gww) significantly reduced intraischemic swelling of cardiomyocytes, but not of capillary endothelial cells. Mitochondrial damage was more pronounced in capillary endothelial cells during ischemia and after reperfusion. Thus, after reversible cardioplegic arrest, structural recovery of cardiomyocytes is better than that of capillary endothelial cells. An incomplete structural protection of capillary endothelial cells may predominantly contribute to postischemic dysfunction in the reperfused heart.

Animals↗

Injury prophylaxis in paragliding.

OBJECTIVES: To show trends in paragliding injuries and derive recommendations for safety precautions for paraglider pilots on the basis of accident statistics, interviews, questionnaires, medical reports, and current stage of development of paragliding equipment. METHODS: All paragliding accidents in Germany have to be reported. Information on 409 accidents was collected and analysed for the period 1997-1999. RESULTS: There was a substantial decrease in reported accidents (166 in 1997; 127 in 1998; 116 in 1999). The number of accidents resulting in spinal injuries was 62 in 1997, 42 in 1998, and 38 in 1999. The most common cause of accident was deflation of the glider (32.5%), followed by oversteering (13.9%), collision with obstacles (12.0%), take off errors (10.3%), landing errors (13.7%), misjudgment of weather conditions (4.9%), unsatisfactory preflight checks (4.9%), mid-air collisions with other flyers (2.2%), accidents during winching (2.2%), and defective equipment (0.5%). Accidents predominantly occurred in mountain areas. Fewer than 100 flights had been logged for 40% of injured pilots. In a total of 39 accidents in which emergency parachutes were used, 10 pilots were seriously injured (26%) and an additional three were killed (8%). CONCLUSIONS: Injuries in paragliding caused by unpredictable situations can be minimised by (a) using safer gliders in the beginner or intermediate category, (b) improving protection systems, such as padded back protection, and (c) improving pilot skills through performance and safety training.

Accidents, Aviation↗

[Anemia, eosinophilia and generalized weakness in a 20-year old African].

CASE HISTORY AND DIAGNOSIS: A 20-year-old African man was admitted to hospital with anemia, eosinophilia, raised liver enzymes and hepatosplenomegaly. Previously, on arrival in Germany, he had undergone a routine medical check-up where simple microscopy of a feces sample as well as serology for lues, AIDS and hepatitis B had all been negative. In our hospital a stool specimen was examined for ova and parasites and revealed ova of Schistosoma mansoni and confirmed the diagnosis of bilharziosis. For the detection of helmintic ova repeated stool examinations with use of concentration techniques are required. Staging by endoscopies, ultrasonography revealed colon pseudopolyposis and periportal fibrosis complicated by portal hypertension and esophageal varices. TREATMENT AND COURSE: Chemotherapy with Praziquantel was effective in eliminating the parasites but in advanced stages chronic fibrotic changes are usually irreversible. Further monitoring will therefore be necessary in our patient. CONCLUSION: Due to increasing migration and international travel, also doctors working in industrialized countries should be aware of tropical diseases.

Adult↗

Personality characteristics of physicians and end-of-life decisions in Russia.

OBJECTIVE: To explore the relationships between personality characteristics, underlying attitudes, and treatment decisions for severely ill elderly patients in a sample of Russian doctors. DESIGN: Survey. SETTING: Group sessions during meetings or individual presentations of questionnaire. SUBJECTS: A convenience sample of 231 physicians from the Archangelsk region in northern Russia who frequently encounter treatment situations with incompetent elderly patients. MEASUREMENTS: Temperament and Character Inventory (Cloninger et al, 1994) for assessing personality dimensions. The questionnaire on decision-making is based on the original developed by Molloy and coworkers from McMaster University in Canada. In a case-vignette, the condition of an 82-year-old man with acute gastrointestinal bleeding is described comprehensively in combination with 3 different levels of information about the patient wishes (no information, DNR order, advance directive). Questions about importance of legal concerns, patient and family wishes, hospital costs, patient's age and level of dementia, and physician's religion for the doctor's decision-making are added. MAIN RESULTS: No significant relationship was found between chosen treatment options and personality traits in any of the 3 situations. However, personality characteristics such as self-directedness, cooperativeness, and self-transcendence, in particular, show significant relationships with attitudes underlying these decisions. CONCLUSIONS: Physicians should be trained to improve their cooperative abilities in the treatment of severely ill elderly patients to be better prepared for their decision-making and coping concerning end-of-life decisions and the use of do-not-resuscitate orders and advance directives. Ethical values in clinical practice, especially patient autonomy, should be addressed during the early stage of the medical curriculum.

Advance Directives↗

Ultrastructure of canine type II pneumocytes during hypothermic ischemia of the lung: a study by means of conventional and energy filtering transmission electron microscopy and stereology.

Alterations in pulmonary surfactant have been reported to be associated with ischemia/reperfusion injury in experimental and clinical lung transplantation. It is unknown whether these alterations are due to damage to surfactant synthesizing type II pneumocytes during hypothermic ischemic storage. The aim of the present study was to examine the effects of hypothermic ischemic storage of the lung on canine type II pneumocytes by means of conventional (CTEM) and energy filtering TEM (EFTEM) and stereology. The lungs of 18 dogs were fixed for TEM immediately after cardiac arrest (6 double lungs) and after storage in Tutofusin at 4 degrees C for 20 min, 4 hr, 8 hr, and 12 hr (6 single lungs, respectively). Using a systematic uniform random sampling scheme, type II pneumocytes were analyzed qualitatively and stereologically. The relative phosphorus content of cell organelles, especially the surfactant containing lamellar bodies, was investigated by EFTEM. By CTEM, no major qualitative alterations could be observed in type II pneumocytes of the experimental groups. Stereologically, no significant changes in the volume densities or the volume-to-surface ratios of type II pneumocytes and their lamellar bodies were found. By EFTEM, the highest intracellular phosphorus signals were recorded over lamellar bodies in all experimental groups. No changes in the phosphorus signals were observed during ischemia. These results indicate that the ultrastructure of canine type II pneumocytes and their lamellar bodies is not affected by hypothermic ischemia of the lung up to 12 hr. Structural preservation of intracellular surfactant is possible during prolonged ischemic lung storage.

Animals↗

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

Chromosomes, Human, Pair 3↗

Discovery of new DNA amplification loci in prostate cancer by comparative genomic hybridization.

BACKGROUND: DNA sequence amplifications are involved in the progression of many tumor types, and have also been found in advanced prostate cancer. The aim of this study was to detect new loci of DNA amplifications in prostate cancer. METHODS: Comparative genomic hybridization (CGH) was used for whole genome screening of DNA sequence copy number alterations in 27 advanced prostate cancers. RESULTS: The most prevalent changes were losses of 8p, 13q (52%, each), 6q (48%), 18q (37%), 5q (30%), 2q, 4q and 16q (26%, each), and gains of 8q (48%), Xq (40%), and Xp (26%). In addition, 16 high-level amplifications were found. These included Xq12 (five), 8q24 (two), and 11q13 (one) with known putative target genes (androgen receptor, MYC and Cyclin D1), and 1q21-25 (three), 10q22 (two), 17q23-24 (two), and 8q21 (one) where the target genes remain unknown. CONCLUSIONS: High-level amplifications at different chromosomal sites occur in advanced prostate cancer. The detection of amplified chromosomal regions may serve as a starting point to discover novel oncogenes involved in prostate cancer progression.

Aged↗

Clinical gene therapy in hematology: past and future.

Gene transfer into hematopoietic cells using viral vectors has focused mostly on lymphocytes and hematopoietic stem cells (HSCs). HSCs have been considered particularly important as target cells because of their pluripotency and ability to reconstitute hematopoiesis after myeloablation and transplantation. HSCs are believed to have the ability to live a long time, perhaps a lifetime, in the recipient following bone marrow transplantation. Genetic correction of HSCs can therefore potentially last a lifetime and permanently cure hematologic disorders in which genetic deficiencies cause the pathology. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target cells. Gene-transfer efficiency of murine HSCs is high using oncoretroviral vectors. In contrast, gene-transfer efficiency using the same viral vectors to transduce human HSCs or HSCs from large animals has been much lower. Although these difficulties may have several causes, the main reason for the low efficiency of human HSC transduction with oncoretroviral vectors is probably because of the nondividing nature of HSCs. Murine HSCs can be easily stimulated to divide in culture, whereas it is more problematic to stimulate human HSCs to divide rapidly in vitro. Because oncoretroviral vectors require dividing target cells for successful nuclear import of the preintegration complex and subsequent integration of the provirus, only the dividing fraction of the target cells can be transduced. This review focuses on gene transfer into human hematopoietic cells, particularly human HSCs. We review the clinical studies that have been reported, including the recent successful gene therapy for X-linked severe combined immunodeficiency. We discuss how the gene-transfer efficiency of human HSCs can be improved using oncoretroviral and lentiviral vectors.

Clinical Trials as Topic↗

The ESTRO-EQUAL Quality Assurance Network for photon and electron radiotherapy beams in Germany.

BACKGROUND: In 1998 an ESTRO Quality Assurance Network for radiotherapy (EQUAL) has been set up for 25 European countries for photon and electron beams in reference and non-reference conditions. MATERIAL AND METHODS: Measurements are done using LiF powder (DTL937-Philitech, France) that is processed with the PCL3 automatic reader (Fimel-PTW). The participating centers irradiate the TLDs with an absorbed dose of 2 Gy according to the clinical routine. RESULTS: Until September 2000 EQUAL has checked 135 photon beams (including the beams rechecked) from 51 radiotherapy centers in Germany out of 86 accepted centers. The results show that 2% of the beam outputs in reference conditions and 3% of the percentage depth doses are outside the tolerance level (deviation > +/- 5%). 6% of the beam output variations and of the wedge transmission factors show deviations > +/- 5%. The global analysis of results shows deviations > +/- 5% in at least one parameter for 18 beams out of the 135 beams checked. Five rechecked beams present one "real dosimetric" problem in one or more parameters, corresponding to 4% of the 114 beams for which the deviations cannot be attributed to set-up errors.--The EQUAL network has checked 89 electron beams in Germany. The results show that all beam outputs checked are within the tolerance level. The standard deviation for the beam output in reference conditions is 2.0% and 2.2% for the beam output for the others field sizes. The percentage of deviations > 3% and < or = 5% for the reference beam output is higher for electron beams than for photon beam checks. Therefore the electron beam calibration and the TPS algorithms should be improved to increase the accuracy of the patient dosimetry for radiotherapy. CONCLUSION: EQUAL program demonstrates a consistency in radiotherapy dosimetry for photon and electron beams resulting in a satisfying accuracy of the dosimetry in Germany.

Cobalt Radioisotopes↗

Attitudinal patterns determining decision-making in severely ill elderly patients: a cross-cultural comparison between nurses from Sweden and Germany.

To explain determinants in the decision-making of nurses in the treatment of severely ill incompetent patients and to describe underlying attitudes, consecutive samples of nurses from Germany and Sweden have been investigated by means of a case scenario and a questionnaire. Whereas the level of dementia emerged as the only factor being significantly related with the treatment option within the Swedish group, patient's age, patient's wishes and ethical concerns were correlated among German nurses. The more the nurses have been able to participate in the provision of the available do-not-resuscitate order or of an advance directive, the less frequent they would perform CPR against the patient's wishes.

Activities of Daily Living↗

Nitroglycerin alters alveolar type II cell ultrastructure after ischemia and reperfusion.

BACKGROUND: Although administration of nitric oxide (NO) has been suggested to reduce pulmonary reimplantation response, concerns remain about cytotoxic side effects. METHODS: Using light and electron microscopy, we examined the effects of the NO donor nitroglycerin (NTG) (0.1 mg/ml) as a supplement to the preservation solution Celsior on the structural integrity of rat lungs after extracorporeal ischemia (4 hours at 10 degrees C) and reperfusion (50 minutes) (IR). We performed evaluation in comparison with Celsior alone after IR using either standard antegrade perfusion through the pulmonary artery or retrograde perfusion through the left atrium as an alternative way to improve the preservation quality. Untreated, non-ischemic lungs served as controls (n = 5 per group). We recorded respiratory and hemodynamic parameters during reperfusion. Tissue collection using systematic uniform random sampling was representative for the whole organ and allowed stereologic quantification of structures. RESULTS: After IR, histochemistry revealed no breaks in the alveolo-capillary barrier and we detected no alveolar flooding. Edema formed in the peribronchovascular cuffs, of which the volume fraction was increased (p =.008). Vasoconstriction of the smaller arteries accompanied antegrade flush, which occurred neither after administration of NTG nor after retrograde flush, as shown by immunostaining for alpha-smooth muscle actin. Treatment with NTG was associated with focal disintegration of Type II cells, which displayed edematous swelling of distinct cell compartments and lysis of mitochondria and cells. Nitroglycerin prevented alveolar collapse, which was increased in the other IR groups (p = 0.013). We observed alterations in intra-alveolar surfactant components. CONCLUSION: These findings indicate pathologic effects of NTG treatment on alveolar epithelial integrity. Therefore, we suggest further critical evaluation of NTG/NO for therapeutic use in lung transplantation.

Animals↗

Forced expression of the Wilms tumor 1 (WT1) gene inhibits proliferation of human hematopoietic CD34(+) progenitor cells.

The Wilms tumor gene (WT1) encodes a zinc-finger containing transcription factor present in primitive hematopoietic progenitor cells. WT1 is also highly expressed in most cases of acute myeloid leukemia. Moreover, WT1 can interfere with induced differentiation of leukemic cell lines. These data suggest a function of WT1 in the maintenance of a primitive phenotype and a role in leukemogenesis by interfering with differentiation, prompting us to investigate its function in human hematopoietic progenitor cells. By retroviral transfer, human CD34(+) cord blood progenitor cells were transduced with a vector encoding either of two splicing variants of WT1, with or without the KTS insert in the zinc-finger domain, linked to expression of green fluorescent protein (GFP) via an internal ribosomal entry site. When compared to cells transduced with vector containing GFP only, WT1 expressing cells showed strongly reduced colony formation in methylcellulose and inhibited proliferation in suspension culture, with no apparent reduction in viability. Cell cycle phase distribution was not affected by WT1 expression. No signs of impaired differentiation, as judged by the surface markers CD11b, CD14 and glycophorin were detected. In contrast to the results with human CD34(+) progenitor cells, the proliferation of murine bone marrow cells was not significantly affected by WT1, consistent with previous data. We conclude that forced expression of WT1 in highly enriched human hematopoietic progenitor cells leads to strong anti-proliferative effects but is compatible with induced maturation of these cells.

Animals↗

[Quality of life of patients with malignant tumors of the head and neck area with special reference to laryngectomy patients].

BACKGROUND: Quality of life is an important factor for patients with cancer in the head and neck region. This factor has not often been investigated in such patients. METHODS: A series of 201 patients with head and neck cancer answered a questionnaire concerning quality of life in general. In addition various parameters of quality of life were rated by an observer such as the Karnofsky scale, the WHO-status and the Spitzer quality of life index. RESULTS: The patients were subdivided into 3 groups, 101 patients with laryngeal cancer, 70 with pharyngeal cancer and 30 others ENT-cancer patients. Patients with cancer of the pharynx had more physical problems. In addition the patients were in different stages of their tumor disease. The patients with cancer in UICC I/II had a better health and quality of life than UICC III/IV. 75% of the whole population spoke about their quality of life as good and better. A similar tendency of quality of life was found in the groups of laryngeal cancer. The indices for health and quality of life in the patients were strongly correlated to the Karnofsky scale, the WHO-status and the Spitzer quality of life index. CONCLUSIONS: The study suggests that it is necessary to measure quality of life variables in head and neck cancer patients. All of the different methods are important for the measurement of quality of life.

Germany↗

Swelling of capillary endothelial cells and cardiomyocytes in the ischaemic myocardium of artificially arrested canine hearts.

To establish whether coronary perfusion with cardioplegic solutions results in better intraischaemic structural preservation of endothelial cells than of cardiomyocytes, we determined intraischaemic swelling of these two cell types in hearts differently arrested during global ischaemia at 5 degrees C. Cardiac arrest was induced in situ by aortic cross clamping or by additional coronary perfusion with various cardioplegic solutions. Parameters for cellular swelling were determined, i.e. barrier thickness of capillary endothelial cells and sum of the volume fractions (V(V)) of free sarcoplasm and mitochondria (V(VSp) + V(VMi)) in cardiomyocytes. In order to test the intraischaemic relative increase of cellular volume in both cell types, regression analyses were performed. The results show that the relative intraischaemic volume increase was similar in both cell types after perfusion with histidine-tryptophan-ketoglutarate solution, and significantly less pronounced in capillary endothelial cells after perfusion with University of Wisconsin solution. In hearts arrested with St. Thomas' Hospital solution, a significantly higher volume increase was determined in capillary endothelial cells. Thus, capillary endothelium does not generally show a higher structural preservation than cardiomyocytes during ischaemia. Instead, volume regulation in both types of cells depends on the type of cardioplegic solution used. These results should be taken into consideration in human transplantation medicine.

Adenosine↗

Osteoid osteoma that occurred in a former fracture site.

Diagnosis of osteoid osteoma often is delayed, despite its high incidence, because of similarities in presenting symptoms with other pathologic entities. The current case report describes a posttraumatic osteoid osteoma. Three years after osteosynthesis of a distal tibial fracture an osteoid osteoma was diagnosed at the former fracture site. After excluding osteomyelitis as a possible diagnosis, the tumor was excised successfully. Based on current knowledge of the pathogenesis of osteoid osteoma, it is unlikely that the lesion observed in the patient was attributable to the previous fracture.

Adolescent↗

The short-EMBU in East-Germany and Sweden: a cross-national factorial validity extension.

The factorial stability and reliability of the 23-item s(hort)-EMBU previously demonstrated to be satisfactory in samples of students from Greece, Guatemala, Hungary and Italy, were extended with 791 students from East-Germany and Sweden. Previous findings on factorial validity, internal reliability and correlations among scales were replicated. The 23-item form thus continues to be recommended as a reliable functional equivalent to the early 81-item EMBU, when the clinical and/or research context does not adequately permit application of time-consuming test batteries.

Adolescent↗