Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).     

Pharmacokinetic profile of piroxicam beta-cyclodextrin, in rat plasma and lymph

1. The absorption of piroxicam into the blood of rats is significantly slower after oral administration of piroxicam beta-cyclodextrin than of free piroxicam. 2. The pharmacokinetic profiles of piroxicam in rat lymph were very similar in both groups. 3. Bioavailability of piroxicam in plasma is higher after treatment with the inclusion product than with free piroxicam. On the other hand, bioavailability in lymph is higher when free piroxicam is administered.     

Quantification of aortic stenosis in mechanically ventilated patients using multiplane transesophageal Doppler echocardiography

OBJECTIVE: The development of sudden postoperative hearing loss as a complication of microvascular decompression (MVD) operations in the cerebellopontine angle has already been reported. A sudden hearing loss of vascular origin may also occur hours or days after such operations, but even in such cases an improvement of hearing over the following weeks is possible. Here we report on a gradual deterioration of hearing over a period of two weeks after MVD which has not been described in the literature up to now. CLINICAL PRESENTATION: A MVD operation was performed twice on a 36 year old patient with trigeminal neuralgia. After the second operation the patient developed a slight hearing impairment 3 days postoperatively which increased over a period of two weeks and ended up with total deafness. The course of intra-operative brainstem auditory evoked potentials and postoperative audiograms is documented. CONCLUSION: Because of gradual development of the delayed hearing loss, we conclude that postoperative tissue scarring may be the underlying pathology.     

Basal catecholamine and cortisol secretion in primary chromaffin cell cultures before and after purification and retroviral transfection

We have investigated the effects of supraphysiological concentrations of catecholamines on glucocorticoid secretion in vitro. These effects were analyzed in adrenocortical cells shown to be present in chromaffin cell cultures as well as in cortical cells cocultured with transfected chromaffin cells that overproduce catecholamines. Cortisol release from residual cortical cells in chromaffin cell cultures was found to be 2.5 times higher than from isolated adrenocortical cells. Removal of the adrenocortical cells from the chromaffin cells resulted in an almost complete cessation of cortisol secretion. Catecholamine overproduction was achieved by transfecting chromaffin cells with the blank retroviral vector pSAM-EN. Coculture of adrenocortical cells with these transfected chromaffin cells further enhanced the stimulating effect of chromaffin cells on cortisol 2.3-fold compared to normal cocultures. In conclusion, cortical cells in chromaffin cell cultures secrete significant amounts of cortisol, which should be considered when evaluating the endocrine function of these cell cultures and which can be abolished by purification. The hormonal activity of adrenocortical cells is highly increased in an environment of catecholamine overproduction, which is of both basic and clinical importance.     

Attributions and behavior in functional and dysfunctional marriages

The study examined whether spouses' attributions for partner behavior are related to their own behavior by assessing their attributions and observing the problem-solving discussions of couples in which (a) neither spouse was depressed or maritally distressed, (b) the wife was depressed and both spouses were maritally distressed, and (c) the wife was not depressed and both spouses were maritally distressed. To the extent they made maladaptive attributions, wives displayed less positive behavior and more negative behavior. Husbands' attributions and behavior were unrelated, and associations between attributions and behavior were not moderated by marital distress and depression. These results highlight the need to clarify how partner behavior contributes to the attributions spouses make and to reexamine interventions designed to modify attributions in marital therapy.     

Visuomotor functions of the lateral pre-motor cortex

Recent studies have provided new insights into the visuomotor functions of the dorsal and ventral regions of the lateral pre-motor cortex. Anatomical and physiological investigations in non-human primates have demonstrated that these regions have differing patterns of cortical connectivity and distinctive neuronal responses. Brain-imaging techniques and lesion studies have begun to probe the functions of homologous regions in humans.     

Metastasizing auricular basal cell carcinoma

Basal cell carcinoma represents the most common skin cancer and involves the head and neck area in 80% to 85% of all patients treated. Despite their frequent occurrence, metastatic spread from these tumors is rare. This paper presents a case of a patient who had a metastasizing basal cell carcinoma. Despite control of primary disease by radical surgery and adjunctive irradiation, bony metastasis was found within nine months of therapy. Palliative therapy was given, but the patient died five months later. The pathophysiology of the metastasizing basal cell carcinomas is described, and a rationale for therapy presented.