Mitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies.

Overaccumulation of abnormally organized mitochondria in so-called "ragged-red" skeletal muscle fibers is a morphological hallmark of mitochondrial myopathies, in particular of mitochondrial encephalomyopathies. Characteristic for the abnormal mitochondria is the occurrence of highly ordered crystalline inclusions. Immuno-electron microscopy revealed that these inclusions react heavily with specific antibodies against mitochondrial creatine kinase (Mi-CK). Image processing of selected crystalline inclusions, sectioned along the crystallographic b, c planes, resulted in an averaged picture displaying an arrangement of regular, square-shaped particles with a central cavity. The overall appearance, dimensions, and symmetry of these building blocks are very reminiscent of single isolated Mi-CK octamers. Taking these findings together, it is concluded that Mi-CK octamers indeed represent the major, if not the only, component of these mitochondrial inclusions.     

Correlation of histological tumor vascularization and Doppler sonography in patients with malignant melanoma of the choroid

Background: In previous studies Doppler sonography was proven to the useful for diagnostics and follow-up of malignant melanomas of the choroid.Methods: To evaluate the correlation between Doppler sonographical findings and the histological tumor vascularization, we examined five eyes of five patients with malignant melanoma of the choroid before enucleation with an ATL Ultramark-8 Duplex scanner and compared these results with computerized planimetry of histological tumor vascularization after immunohistochemical staining of vascular endothelium with anti-factor-VIII antibodies.Results: We found no definite correlation of flow velocities with histological parameters of tumor vascularization. The tendency was for a decrease in maximum flow velocities as histological vascularization increased.Conclusions: Due to (1) the usual lack of sensitivity parameters of the used Duplex device for the clinical user and (2) the unpredictable branching pattern within a melanoma resulting in an unknown angle of incidence of the Doppler beam, we conclude that the quantitative results of Doppler sonography require cautious interpretation. Nevertheless, presence or absence of Doppler shifts is a valuable parameter for the follow-up of irradiated tumors.Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, 1992     

Psychomotor retardation and anhedonia in depression

Anhedonia, the inability to experience pleasure, and observed changes in psychomotor performance are frequent psychopathological phenomena in major depression with possible common neurobiological mechanisms. Interest, pleasure and reactivity to pleasurable stimuli contribute to movement generation and observable behaviour. Therefore the relationship between anhedonia and psychomotor retardation was studied in 48 depressed patients. Subjectively experienced anhedonia correlated with self-rated but not with observer-rated global severity of depression. There was a significant correlation between anhedonia and psychomotor retardation assessed with the Widlöcher Retardation Scale. The results suggest the existence of an empirical relationship between reduced ability to experience pleasure and observable psychomotor retardation in depression. Specific measures of psychomotor phenomena may provide further insights into the relationship between observable behaviour and self-experienced symptoms in depression.     

The processing of secretogranin II in the peripheral nervous system: release of secretoneurin from porcine sympathetic nerve terminals

The distribution of secretoneurin (SN), a peptide derived from secretogranin II (SgII), in the coeliac ganglion, the splenic nerve and the spleen was examined by immunohistochemistry. In the ganglion, SN immunoreactivity (IR) was unevenly distributed. Positive nerve terminals densely surrounded some postganglionic perikarya in which also intense SN-IR was present. In the crushed splenic nerves, intense immunoreactivities appeared proximal (but to a less extent also distal) to the crush of the nerve. Analysis by cytofluorimetric scanning (CFS) demonstrated that SN-IR and neuropeptide Y immunoreactivity (NPY-IR) were predominant in the axons proximal to the crush representing anterogradely transported components. Using radioimmunoassay (RIA) we demonstrated that upon electrical stimulation (10 Hz, 1 min) of the splenic nerve, significant amounts of SN-IR (64.2+/-2.3 fmol) were released together with NA (4. 1x106+/-0.2 fmol) and NPY (330.0+/-7.2 fmol) from the isolated perfused porcine spleen. To evaluate the processing of SgII in sympathetic neurons, boiled tissue extracts (coeliac ganglia and splenic nerve) and boiled spleen perfusate (used as a suitable source for vesicle derived peptides) were analysed by gel filtration chromatography followed by SN-RIA. In all cases immunoreactivity was present solely as SN, indicating that SgII was fully processed to the free peptide. The evidence that SN is transported to the nerve terminals and is released from the porcine spleen upon nerve stimulation, suggests that it may modulate adrenergic neurotransmission and may also play a role in the neuroimmune communication.     

Efficiency of continuous positive airway pressure versus theophylline therapy in sleep apnea: comparative sleep laboratory studies on objective and subjective sleep and awakening quality

Sleep apnea is the most common sleep-related breathing disorder characterized by repetitive episodes of hypoxemia. Therapies include behavioral, surgical, orthodontic, pneumological, and pharmacological interventions. The aim of the present study was to compare the efficiency of pneumological therapy by nasal continuous positive airway pressure (CPAP) versus a pharmacological approach with theophylline (Respicur retard(R) 400 mg) on respiratory variables as well as objective and subjective sleep and awakening quality in patients with moderate sleep apnea measured by polysomnography and psychometry. Under CPAP therapy all respiratory variables improved and normalized, while under theophylline only the apnea-hypopnea index and the desaturation index improved but still did not return to normal values. Regarding sleep initiation and maintenance, CPAP therapy prolonged sleep latency and reduced movement time, while patients treated with theophylline showed reduced total sleep period, total sleep time and sleep efficiency. Sleep architecture demonstrated an increase in deep sleep and REM stages under CPAP therapy, and remained unchanged under theophylline. Concerning subjective sleep and awakening quality, both treatments improved well-being in the morning. Regarding objective awakening quality, reaction time performance was improved in both groups. In conclusion, CPAP treatment is more effective than theophylline regarding respiratory variables as well as the normalization of sleep maintenance and sleep architecture in sleep apnea patients.     

Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF) in meningitis and hemorrhage

Using echographic flow imaging (colour Doppler), flow within ventricular CSF-pathways was discovered in an infant with purulent meningitis. 22 mature and 40 premature infants were then investigated for presence of CSF-flow which was detected in a further 5 infants, all premature. Diagnostic criteria for echographic CSF-flow imaging are: 1. flow signals "within" CSF-pathways; 2. to-and-fro movement of CSF (spectral analysis); 3. specific response of CSF-flow to stimuli (respiration, crying, abdominal palpation); 4. dynamic CSF-imaging related to specific anatomical areas of intracranial CSF-pathways. Echographic detection of CSF-flow depends on optimized adjustment of controls, equipment used, meticulous examination technique and awareness of pitfalls on the part of the examiner. A further prerequisite is the presence of scattering particles within CSF, such as red or white blood cells (minimum concentration in the order of one thousand cells/microL) or air. Although echographic CSF-flow imaging is not applicable for excluding the presence of disease, it appears to be a new diagnostic tool with considerable potential allowing selected early and non-invasive diagnosis of CSF-pathology and giving new insights into CSF-hemodynamics.     

10. Einführung zum Thema

Zusammenfassung Der fortgeschrittene Organkrebs ist eine systemische Krankheit. Die chirurgische Therapie mu durch interdisziplinäre Kooperation ergänzt werden. Jetzt gilt es, entsprechende Arbeitsgemeinschaften zu bilden, um die heute und morgen gegebenen Möglichkeiten standardisierter Chirurgie, Chemotherapie, Radiotherapie, immunologischer Therapie und Rehabilitation optimal nutzen zu können. Eine einheitliche Dokumentation nach dem TNM-System ist dabei eine notwendige Voraussetzung.