[Protein-losing enteropathy: a cause of hypoalbuminaemia in patients with systemic lupus erythematosus]. / Enteraler Proteinverlust als Ursache einer schweren Hypoalbuminämie bei systemischem Lupus erythematodes.

Lupus nephritis is the most common cause of extended edema and hypoalbuminemia in patients with systemic lupus erythematosus (SLE). However, the same immune complex mechanisms which lead to renal protein loss can also be active in the gastrointestinal tract, resulting in severe hypoproteinemia through enteral protein loss. The case of a young female patient with otherwise mild SLE and severe hypoproteinemia through bowel manifestation of the disease is presented here. No gastrointestinal symptoms such as diarrhoea were present, but immunohistology of the smaller and larger bowel showed severe immunocomplex disease with focus on the submucosa and the basal membrane. Other causes of hypoproteinemia were excluded. Treatment with prednisolone and azathioprine led to fast and durable resolution of symptoms.

Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study.

OBJECTIVES: Combined treatment approaches targeting tumor as well as other cells contributing to tumor progression may control chemorefractory malignancies. METHODS: A phase II trial was initiated to analyze the activity of continuously administered pioglitazone and rofecoxib combined with low-dose chemotherapy (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma or anaplastic glioma). RESULTS: Fourteen patients were evaluable for response and toxicity. Major side effects were palmoplantar erythema, edema and motor neuropathy grade 3. Disease stabilizations lasting longer than 3 months were noted in 4 of 14 patients (29%). Clinical responses did not correspond to immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator-activated receptor-gamma and CD31. DISCUSSION: The study demonstrates that this novel regimen is moderately active and well tolerated in patients with high-grade gliomas. As a comparably small proportion of patients responded, the regimen might only be suitable for a subset of highly selected patients.

Reactive microglia in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is characterized by a loss of neurons accompanied by astrogliosis and spongiform changes in the neuropil. It has been recognized that reactive microglia occur in CJD but little is known about the regional distribution and extent of the microglial activation. We have, therefore, examined six brains from cases of sporadic CJD by immunohistochemical labelling of grey and white matter microglia from frontal, parietal, temporal, and occipital lobes, striatum, thalamus, cerebellum and brain stem with RCA-1, LCA, CD68, HLA-DR, and HAM56. Microglial activation occurred in the grey matter where astrogliosis and prion protein (PrP) deposits were prominent. Processes of activated microglia surrounded the outer rim of spongy vacuoles. A diffuse microglial response was seen in the white matter that was immunophenotypically different from grey matter. Double-labelling with microglial markers and anti-PrP showed that activated microglia did not contain PrP-immunoreactivity. Therefore a primary role of microglia in PrP processing seems unlikely. Activated microglia may contribute to neuronal damage in CJD due to their cytotoxic potential.

Atypical and anaplastic meningiomas--does the new WHO-classification of brain tumours affect the indication for postoperative irradiation?

We retrospectively analysed 13 patients (pts.) treated at the University of Tübingen from 1985 to 1993 to evaluate the results of radiation therapy (XRT) given as an adjuvant to totally or subtotally resected meningiomas. The overall survival was 38% at five years with a probability of relapse of 50% at this time. Reclassification of the tumours according to the new WHO-classification of brain tumours [14] revealed 10 grade-II-tumours (atypical meningioma) and 3 grade-III-tumours (anaplastic meningioma). Radiotherapy failed in all 3 pts. with macroscopically incomplete resection (Simpson's grade IV), who died with relapse between 4 and 51 months after radiotherapy. 5 out of 10 pts. with grade-II-tumours relapsed. All 3 pts. with grade-III-tumours died with relapse between 6 and 21 months after XRT. Morbidity was seen in 2 pts. after irradiation with 60 GY (ICRU dose specification). Complete surgical exstirpation offers the best possibility of tumour control. Grade-III-tumours should be irradiated whatever the extent of the primary surgery was. Our results might indicate a possible indication for XRT in pts. with atypical grade-II-tumours especially when radical surgery must be in doubt. Prospective multicentre trials are warranted to prove the prognostic value of the new WHO-classification for atypical and anaplastic meningiomas and to define the ultimate role of radiotherapy in this setting.

Freeze-fracture analysis of endothelial cell membranes in rabbit carotid arteries subjected to short-term atherogenic stimuli.

Endothelial cell membranes of rabbit carotid arteries were examined by the freeze-fracture technique. In the normal endothelium the mean densities of membrane-bound vesicles were 75 vesicles/microns 2 on the luminal cell membrane and 102 vesicles/microns 2 on the abluminal membrane. Whilst the vesical openings on the luminal membrane were randomly distributed those on the abluminal membrane were typically ordered in a macular pattern with lines free of vesicles. Tight and gap junctions between endothelial cells were numerous. After stimulating the carotid arteries with weak electrical impulses, a technique used to induce enhanced endothelial permeability and the formation of atheromatous plaques after repeated stimulations (Betz et al. 1985), vesicle openings were reduced to 78 vesicles/microns 2 on abluminal membranes. Membranes on the luminal side and intercellular tight and gap junctions remained unchanged.

Structural alterations in vascular endothelial tight junctions in the course of their gradual degradation in vitro.

Rabbit aorta explants in organ culture maintained their endothelium as a confluent cell layer for 1-6 days. Depending on culture time, interendothelial tight junctions underwent gradual morphological changes in their substructure, as seen in freeze-fracture replicas. The formation of a P-face associated groove and concurrent confluence of tight junction particles on E-faces after 24 hr in vitro was followed by a rarefaction of particles and shortening of tight junctional strands. By day 6 in vitro, almost all tight junctions have disappeared. We interpret these findings as signs of a degradation of tight junctions in vitro, involving three different substructural components: a component facing the protoplasm, tight junction particles and a component facing the extracellular space. The degradation was inhibited by culturing under increased ambient pressure (910 mmHg).