Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle

Human Molecular Genetics     

Isolated congenital dislocation of the radial head: Good function in 4 untreated patients after 14-45 years

4 patients with a mean age of 20 years and isolated congenital radial head dislocation (1 unilateral anterior, 1 unilateral posterior and 2 bilateral anterior dislocations) were all pain-free and had almost normal elbow function.     

Ganglioglioma: A clinicopathological study of 10 cases

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto-medial, bifrontal, temporal, temporo-basal, temporo-parieto-occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki-67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio- and chemotherapy is still controversial.     

Cavernous hemangioma of the mediastinum

After presenting an own case of a cavernous hemangioma of the mediastinum, the clinical pattern, differential diagnosis, diagnostic procedure (computed tomography), and therapy of this rare tumor form are described.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Plasma hypercoagulability in haemodialysis patient: impact of dialysis and anticoagulation

Background: Thrombotic complications are common in patients with endstage renal disease and contribute substantially to the morbidity and mortality in this population. The aim of the present study was to: I) determine the prevalence and the extent of hypercoagulability in patients undergoing dialysis treatment by measuring parameters that directly reflect thrombin concentrations, ii) assess changes in coagulation status during haemodialysis (HD); iii) quantify the relative impact of heparin, dialysis and their combined effects on coagulation status and iv) detect factors that modify coagulation haemostasis in dialysis patients. Method: A total of 39 patients (HD: n=29, CAPD: n=10) was analysed for procoagulatory and fibrinolytic activity determined by measurements of partial thromboplastin time, prothrombin fragments F1+2, thrombin-antithrombin complexes and D-dimer concentrations. HD patients were investigated prior to and during dialysis. A subgroup of patients was infused heparin alone without dialysis or was dialysed without heparin administration. Furthermore, subgroup and correlation analyses were performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V, underlying disease and treatment with recombinant erythropoietin (rhEPO). Results: Baseline levels of all parameters-procoagulatory and fibrinolytic- were substantially elevated in all patients, but to a higher degree among those on CAPD. Moreover, haemodialysis treatment increased procoagulatory markers even further, suggesting stimulated coagulation and/or insufficient anticoagulation during dialysis. However, after 3 h of dialysis thrombin concentrations, determined by quantification of prothrombin fragments, were inversely correlated with Kt/V. Selective heparin infusion diminished procoagulatory activity only slightly and incompletely, whereas HD without heparin resulted in excess thrombin accumulation. Finally, subgroup analyses revealed more pronounced thrombin formation among patients treated with polysulfon dialyzers, whereas erythropoietin dosage was positively related with lower procoagulatory activity. Conclusion: A majority of patients on dialysis are in a hypercoagulable state, which is further aggravated by the haemodialysis procedure itself and may not be sufficiently controlled with current anticoagulation regimens. Intensified heparin treatment and the use of rhEPO are likely to improve coagulation haemostasis, whereas the type of dialyzer should be considered as a relevant procoagulatory factor.     

In vitro evaluation of ablation parameters of normal and fibrous aorta using smooth excimer laser coronary angioplasty

A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm² in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc.