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Notes: [Auszug] Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy ...

Notes: [Auszug] Many galaxies are thought to have supermassive black holes at their centres—more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the ...

Notes: Summary Objective The aim of this prospective study was to describe a collective of patients with respect to the manifestation of multiple organ failure in operative and non-operative intensive care units.¶   Methods: Included were all patients treated longer than 48 hours in a participating intensive care unit. Basic epidemiologic data and physiological parameters were recorded and three different score values (SOFA, Moore and Goris scores) were calculated for each day in the intensive care unit and presented according to the particular specialty. A delta score value for each patient was calculated from the first and last recorded value and was compared to the outcome of the patient (survivor/non-survivor). With the Kohen-Kappa coefficient the daily change of the score value relating to an improvement or deterioration was referred to the clinical assessment. Further statistical analysis was performed with Mann-Whitney U test and by means of ANOVA.¶   Results: 443 patients were included and 4880 observation days were recorded. There was an over-representation of operative patients (general surgery (119 pat.), trauma surgery (163 pat.), neurosurgery (82 pat.)) compared to non-operative patients (medicine (49 pat.), neurology (19 pat.)). Survivors stayed 8 and non-survivors 6 days in the intensive care unit. Overall mortality was 17.3%.¶   Non-operative specialties had a higher mortality with a significantly higher Goris multiple organ failure score on admission for neurologic patients and a higher Goris multiple organ failure score for medical patients (not significant) compared to operative patients.¶   The delta SOFA score value is the most powerful to indicate survival or death compared to the other two delta scores. The Goris score on admission produces statistically significant differences concerning survivors and non-survivors even without the gastrointestinal and central nervous system, but is unreliable considering the delta score.¶   Conclusion: In the present investigation, a basic data set for patients from six different medical specialties were collected and compared. Faculty-specific differences between sets of patients and mortality were shown. This will have consequences for stratifying groups of patients for further interdisciplinary investigation. Clinical assessment of the incidence of multiple organ failure and clinical assessment of changes in daily multiple organ failure status were poorly mirrored by all scores under surveillance. Considering delta score values, the SOFA score is the most reliable score for interdisciplinary description of survival or non-survival. Although the SOFA score seems most reliable for describing a patient‘s clinical course, there is a need for the development of a comprehensive, interdisciplinary score for assessment of multiple organ failure.

Notes: Summary The diagnosis of an acute partial tear of the anterior cruciate ligament was made in 56 patients who did not undergo surgical repair. After a period of up to 5 years, 39 returned for follow up evaluation. They were divided into three groups according to clinical analysis of the knee and the Lysholm-Gillquist score. Our aim was to determine their long term functional limitations. 56% had progressed to anterior cruciate ligament deficiency at the time of follow up. This came about not only after resuming sporting activities, but also occurred in those who were not so active. Our results suggests that a partial tear leaves an irreversible defect which may progress to a complete tear, especially in young athletes engaged in active sport.

Notes: Abstract Resistance to cytotoxic chemotherapy is a major problem in the management of patients with metastatic breast cancer. Various data suggest P-glycoprotein-associated multidrug resistance (MDR) to be a relevant resistance mechanism in this tumor. The purpose of this study was to evaluate feasibility and activity of combining oral dexverapamil, a second-generation chemosensitizer currently in clinical development for MDR reversal, with epirubicin in patients with epirubicin-refractory high-risk metastatic breast cancer. Patients first received epirubicin alone at 120 mg/m2. In cases of clinical refractoriness, epirubicin was continued at the same dose and schedule but supplemented with oral dexverapamil. Dexverapamil was given at 300 mg every 6 h for a total of 13 doses and commenced 2 days prior to epirubicin administration. At the time of this interim analysis, 41 patients had received epirubicin alone and 20 proceeded to treatment with epirubicin plus dexverapamil. Of the 20 patients, 14 were considered evaluable for toxicity and activity. Addition of dexverapamil resulted in a significant decrease in mean heart rate and blood pressure as well as prolongation of PQ time as compared to epirubicin alone. However, these cardiovascular effects of dexverapamil were usually mild, and subjective tolerance of treatment was good. In 7/14 patients, dose escalation of dexverapamil was feasible. Dexverapamil had no effect on epirubicin toxicities and did not require reduction of the epirubicin dose. In 2/14 patients, the addition of dexverapamil to epirubicin was able to convert progressive disease and no changes respectively, into partial responses. In 3 patients with progressive disease, addition of dexverapamil temporarily prevented further tumor progression. Analyses of dexverapamil and nor-dexverapamil plasma levels, of in vitro reversal activity of patient sera containing dexverapamil, and of epirubicin pharmacokinetics without and with dexverapamil are currently in progress. Addition of oral dexverapamil to epirubicin 120 mg/m2 proved to be feasible in a multiinstitutional setting. Patient accrual is continuing to determine whether dexverapamil is capable of overcoming epirubicin refractoriness in a significant number of patients with metastatic breast cancer.

Notes: Abstract A 64-year-old female patient has been suffering from sinus histiocytosis with massive lymphadenopathy (SHML) for 2 years. After 12 months of illness, the patient developed swelling and pain in various skeletal regions. Scintigraphic, radiological and CT imaging revealed multiple osseous lesions. Subsequent biopsies yielded the histomorphological findings typical for SHML. After operative resection of the left cuboid, which was the most painful region during walking, the defect was filled with an autologous bone transplant. At this time no other osteolytic region was treated surgically, because the patient had first to undergo ENT treatment.

Notes: Abstract Resistance to cytotoxic chemotherapy continues to be a major obstacle to more effective treatment of human cancers. A particular problem in clinical cancer chemotherapy is the phenomenon of simultaneous resistance of cancers to a variety of unrelated cytotoxic agents. Such resistance to multiple drugs is observed much more often than resistance to individual compounds. A similar experimental phenomenon has been termed multidrug resistance or MDR. Much has been learned in recent years about molecular mechanisms which can lead to MDR in cancer cells and a number of studies has been performed to evaluate the clinical relevance of such mechanisms. In particular, P-glycoprotein-associated MDR (MDR1) has received a lot of attention. This review will discuss (i) some principal aspects of drug resistance in cancer with particular emphasis on MDR1; (ii) available data on drug resistance mechanisms in brain tumors; and (iii) our current knowledge on the putative role of P-glycoprotein in the blood-brain barrier.

Notes: Abstract Background: Tumor volumes of more than 100 ml and the presence of primary metastases have been identified as determinants of poor prognosis in patients with Ewing tumors. We sought to assess the prevalence of critical tumor size and primary metastases in a large national sample of patients at the time of first diagnosis and to identify factors that are associated with their occurrence. Patients: The present report is based on data of 945 German patients who were enrolled into the (EI)CESS therapy studies between 1980 and 1997. It is assumed that registration of German patients with Ewing tumors under the age of 15 years was almost complete since around 1985. Diagnoses of primary tumors were ascertained exclusively by biopsies. Analyses were restricted to patients with Ewing tumors of bone due to the few occurrences in soft tissues. Methods: Tumor volume data as assessed by radiography, computed tomography or nuclear magnetic imaging were available for 821 patients. The diagnosis of primary metastases was based on thoracic computed tomography or on whole body bone scans in 936 patients. Suspicious lesions had to be confirmed by bone marrow biopsies. We explored how year of first diagnosis, age at first diagnosis, sex, histological subtype and site of the primary tumor related to tumor size and presence of metastases by univariate and multivariate statistical techniques. Results: Sixty-eight percent of the patients (n = 559) had a volume above 100 ml with smaller tumors being more common in childhood than in late adolescence and early adulthood. Extensive volumes were observed in almost 90% of the tumors located in femur and pelvis while they were less common in other sites (P 〈 0.001). On average, 26% of all patients presented with clinically apparent primary metastases. The detection rate of metastases was markedly higher in patients diagnosed after 1991 (P 〈 0.001). Primary metastases were also significantly more common for tumors originating in the pelvis and for peripheral neuroectodermal tumors (PNET; P 〈 0.01). Tumors greater than 100 ml were positively associated with metastatic disease (P 〈 0.001). Multivariate analyses, which included simultaneously all univariate predictors in a logistic regression model, indicated that most of the observed associations were essentially unconfounded. The adjusted odds ratios (OR) for the presence of tumor volumes ≥100 ml were OR = 1.5 per age rise of 10 years, and OR = 5.8 for pelvis and OR = 7.1 for femur as primary tumor site (all P 〈 0.001). The presence of metastases was significantly associated with the year of diagnosis (OR = 1.9, after 1991 vs. before 1986), pelvis as site of the primary tumor (OR = 1.8), a PNET (OR = 1.5), and tumor size ≥100 ml (OR = 1.6). Conclusions: In conclusion, we find that the prevalence of established factors for an unfavorable prognosis is disturbingly high among patients diagnosed with Ewing tumors. Recent progress in imaging techniques seems to account for much of the rise in the detection rate of metastases after 1991. We identify age and, in particular, pelvic and femoral site as the major determinants of local tumor extension. Occurrence of primary metastases is independently related to tumor size, pelvic site, and PNET.