Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Abstract: OBJECTIVES: Recently, recurrent mutations in regulatory DNA regions, such as promoter mutations in the TERT gene were identified in melanoma. Subsequently, Weinhold et al. reported SDHD promoter mutations occurring in 10% of melanomas and being associated with a lower overall survival rate. Our study analyzes the mutation rate and clinico-pathologic associations of SDHD promoter mutations in a large cohort of different melanoma subtypes. METHODS: 451 melanoma samples (incl. 223 non-acral cutaneous, 38 acral, 33 mucosal, 43 occult, 43 conjunctival and 51 uveal melanoma) were analyzed for the presence of SDHD promoter mutations by Sanger-sequencing. Statistical analysis was performed to screen for potential correlations of SDHD promoter mutation status with various clinico-pathologic criteria. RESULTS: The SDHD promoter was successfully sequenced in 451 tumor samples. ETS binding site changing SDHD promoter mutations were identified in 16 (4%) samples, of which 5 mutations had not been described previously. Additionally, 5 point mutations not located in ETS binding elements were identified. Mutations in UV-exposed tumors were frequently C〉T. One germline C〉A SDHD promoter mutation was identified. No statistically significant associations between SDHD promoter mutation status and various clinico-pathologic variables or overall patient survival were observed. CONCLUSIONS: Melanomas harbor recurrent SDHD promoter mutations, which occur primarily as C〉T alterations in UV-exposed melanomas. In contrast to the initial report and promoter mutations in the TERT gene, our analysis suggests that SDHD promoter mutations are a relatively rare event in melanoma (4% of tumors) of unclear clinical and prognostic relevance.
    Type of Publication: Journal article published
    PubMed ID: 26327518
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: The majority of human tumours can be easily and correctly diagnosed based on clinical information and pathological assessment. In some cases however, correct diagnosis can prove difficult. In such cases, molecular approaches can be of significant diagnostic value. In recent years, the understanding of genetic alterations has greatly increased. In cutaneous melanoma, it is now well recognised, that 70-80% of tumours harbour BRAF and NRAS mutations. These mutations never occur in uveal melanoma. On the other hand activating GNAQ and GNA11 mutations are found in approximately 90% of uveal melanomas, and are exceptionally rare in other melanomas (〈1%). Here, we demonstrate a number of melanoma cases, where distinguishing if a tumour was of cutaneous or ocular origin was not possible based on clinical and pathological assessment. In these cases there was either atypical clinical presentation or metastasis of unclear primary. Histological distinction between uveal and cutaneous melanomas, especially at the stage of metastasis, is not reliable as they can be morphologically very similar. In all cases we present, a simple genetic assessment of oncogene mutation status was able to clearly define the melanoma type. This type of genetic assessment is of great diagnostic value and due to its simplicity could be performed in routine clinical practice even in smaller institutions.
    Type of Publication: Journal article published
    PubMed ID: 26918736
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-1238
    Keywords: Lateral posture ; Hemodynamic effects ; Kinetic therapy ; Respiratory failure ; Kight ventricular function ; Atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To quantify the hemodynamic effects of turning critically ill, mechanically ventilated patients to the extreme left and right lateral postures. Design Prospective investigation. Setting Eight-bed intensive care unit in a university hospital. Patients Twelve consecutive patients presenting with severe respiratory failure and requiring continuous positive inotropic support. Interventions All patients were mechanically ventilated and placed in a kinetic treatment system. They were positioned in the supine, left dependent, and right dependent postures, resting for 15 min in each position. Measurements and results Hemodynamic measurements, assessments of right ventricular function, and determinations of intrathoracic blood volume were performed in three different positions. Concentrations of atrial natriuretic peptide in plasma were quantified. In three patients, the findings were controlled by transesophageal echocardiography. Cardiac index [median (range) 5.5 (3.2–8.1) vs 4.3 (3.2–7.5) l/min per m2,p〈0.01], intrathoracic blood volume [1125 (820–1394) vs 1037 (821–1267) ml/m2,p〈0.01], and right ventricular end-diastolic volume [130 (83–159) vs 114 (79–155) ml/m2,p〈0.05] increased significantly in the left dependent position compared to supine. Mean arterial pressure did not change. Atrial natriuretic peptide levels rose from 140 to 203 pg/ml. In the right dependent position, we found a marked decrease in the mean arterial pressure [85 mmHg (supine) to 72 mmHg (right dependent),p〈0.01]. Cardiac index and intrathoracic blood volume were unchanged, but right ventricular enddiastolic volume decreased from 114 to 102 ml/m2 (p〈0.05) Additionally, atrial natriuretic peptide levels decreased significantly (median Δ value: 37 pg/ml). In echocardiographic controls we found an increase in right ventricular end-diastolic diameters in the left dependent position and shortened diameters in the right dependent position. Conclusions Extreme lateral posture affects the cardiovascular system in critically ill, mechanically ventilated patients: in the left dependent position a “hyperdynamic state” is reinforced, while the right decubitus position impairs right ventricular preload and predisposes to hypotension. Echocardiography and changes in plasma atrial natriuretic peptide values indicate that these findings are due to altered distensibility of the right ventricle caused by regional intrathoracic gravitational changes. We conclude that the duration and the angle of lateral posture should be restricted in hemodynamically unstable patients.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-1238
    Keywords: Key words Lateral posture ; Hemodynamic effects ; Kinetic therapy ; Respiratory failure ; Right ventricular function ; Atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To quantify the hemodynamic effects of turning critically ill, mechanically ventilated patients to the extreme left and right lateral postures. Design: Prospective investigation. Setting: Eight-bed intensive care unit in a university hospital. Patients: Twelve consecutive patients presenting with severe respiratory failure and requiring continuous positive inotropic support. Interventions: All patients were mechanically ventilated and placed in a kinetic treatment system. They were positioned in the supine, left dependent, and right dependent postures, resting for 15 min in each position. Measurements and results: Hemodynamic measurements, assessments of right ventricular function, and determinations of intrathoracic blood volume were performed in three different positions. Concentrations of atrial natriuretic peptide in plasma were quantified. In three patients, the findings were controlled by transesophageal echocardiography. Cardiac index [median (range) 5.5 (3.2–8.1) vs 4.3 (3.2–7.5) l/min per m2, p〈0.01], intrathoracic blood volume [1125 (820–1394) vs 1037 (821–1267) ml/m2, p〈0.01], and right ventricular end-diastolic volume [130 (83–159) vs 114 (79–155) ml/m2, p〈0.05] increased significantly in the left dependent position compared to supine. Mean arterial pressure did not change. Atrial natriuretic peptide levels rose from 140 to 203 pg/ml. In the right dependent position, we found a marked decrease in the mean arterial pressure [85 mmHg (supine) to 72 mmHg (right dependent), p〈0.01]. Cardiac index and intrathoracic blood volume were unchanged, but right ventricular end-diastolic volume decreased from 114 to 102 ml/m2 (p〈0.05) Additionally, atrial natriuretic peptide levels decreased significantly (median Δ value: 37 pg/ml). In echocardiographic controls we found an increase in right ventricular end-diastolic diameters in the left dependent position and shortened diameters in the right dependent position. Conclusions: Extreme lateral posture affects the cardiovascular system in critically ill, mechanically ventilated patients: in the left dependent position a ”hyperdynamic state“ is reinforced, while the right decubitus position impairs right ventricular preload and predisposes to hypotension. Echocardiography and changes in plasma atrial natriuretic peptide values indicate that these findings are due to altered distensibility of the right ventricle caused by regional intrathoracic gravitational changes. We conclude that the duration and the angle of lateral posture should be restricted in hemodynamically unstable patients.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-055X
    Keywords: Schlüsselwörter: Hospitalmortalität – Intensivtherapie – APACHE-II-Score – APACHE-III-Score – Glasgow Coma Scale ; Key words: Hospital mortality – Intensive care medicine – APACHE II score – APACHE III score – Glasgow Coma Scale
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. The Acute Physiology and Chronic Health Evaluation model (APACHE II, APACHE III) is used to describe the severity of illness and predict the outcome in critically ill patients. APACHE III, introduced in 1991, has not yet been validated in Europe. We calculated APACHE II and APACHE III scores in patients after admission to the intensive care unit (ICU) and compared the prognostic value on hospital mortality. Method. One hundred fifty patients with stay of over 24 h were enrolled in the study and prospectively and consecutively investigated. APACHE II and III scores were calculated as described by the authors. The mean and median values of the survivors were compared with the non-surviving group (Mann-Whitney U test). Receiver operating characteristics (ROC analysis) and the areas under the ROC curves were plotted. Results. Of the 150 patients, 34 died during their hospital stay (22.7%). The mean and median APACHE II and III scores were significantly higher (P〈0.001) in the non-surviving group. The area under the ROC curve was higher for APACHE III (0.899) compared to APACHE II (0.847). Conclusions. APACHE II and APACHE III were both found to have good prognostic value in general ICU patients. Our results suggest that the APACHE III version includes a more precise prediction of hospital mortality than APACHE II. A new aspect of APACHE III is an expanded modification of the Glasgow Coma Scale to assess neurologic derangements.
    Notes: Zusammenfassung. Wir verglichen die neue Version des "Acute Physiology and Chronic Health Evaluation" (APACHE-III) Scores mit der bekannten und etablierten Version APACHE-II, indem wir die Schwere von Erkrankungen oder Verletzungen bei 150 Patienten nach deren Aufnahme auf die Intensivstation mittels beider Scores ermittelten. Die Mittel- und Medianwerte der Patientengruppe, die überlebte, waren für beide Scores signifikant niedriger (p〈0,001, Mann-Whitney-U-Test) im Vergleich zu den Patienten, die im Verlauf der Hospitalphase verstarben. Der durch das Verfahren der "receiver operating characteristics analysis" (ROC-Analyse) vorgenommene statistische Vergleich der prognostischen Qualität ergab für APACHE-III eine noch höhere Genauigkeit (Fläche unter der ROC-Kurve=0,899) im Vergleich zu APACHE-II (0,847). Nach unseren Ergebnissen ist APACHE-III genauso gut geeignet wie APACHE-II, den Erkrankungsgrad von Intensivpatienten zu charakterisieren. Weitere Untersuchungen müßten zeigen, ob APACHE-III – wie in unseren Befunden angedeutet – noch präziser das Mortalitätsrisiko zu prognostizieren vermag als APACHE-II.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 0942-0940
    Keywords: Head injury ; S-100 protein ; NSE ; outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the time course of neuron specific enolase (NSE) and S-100 protein after severe head injury in correlation to outcome. We included 30 patients (GCS〈9), who had been admitted within 5 hours after injury, in a prospective study. Blood samples were taken on admission, 6, 12. and 24 hours and every 24 hours up to the fifth day after injury. The outcome was estimated on discharge using the Glasgow Outcome Scale. 70% reached a good outcome. All concentrations of NSE and 83% of the S-100 samples were elevated concerning the first probe (30.2 μg/l NSE mean and 2.6 μg/l S-100 mean). Patients with bad outcome had an NSE concentration of 38 μg/l (mean) compared with 26.9 μg/l (mean) in patients with good outcome. Patients with bad outcome had an S-100 concentration of 4.9 μg/l (mean) compared with 1.7 μg/l (mean) in patients with good outcome (p〈0.05). The mean values of NSE and S-100 decreased during the first 5 days. Four patients with increasing intracranial pressure showed a quick increasing concentration of NSE, in two patients the S-100 level showed a slower rise. The NSE serum levels did not correlate with intracranial pressure values. Our results show that the first serum concentration of S-100 seems to be predictive for outcome after severe head injury.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...