Technical improvements in the clotted plasma droplet MIF assay in vitro.

The migration inhibitory activity of culture supernatants of rat and human lymphocytes stimulated with PHA and Con A-Sepharose was tested on cell migration from clotted plasma droplets. This technique was improved by using homologous as well as heterologous plasma and fibrinogen solutions for suspending the migratory cells, automatic micropipettes for performing the technique and purified cell populations as target. The effects of calcium chloride and of the cell concentration in the plasma droplets on the migration indices obtained in the MIF assay were tested.     

ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats

The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model of malignant hypertension which lead to secondary alterations of the extracellular matrix. Our aim was to determine ACE-inhibitor related changes of proteases involved in the reconstruction of the extracellular matrix in the brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated with either an antihypertensive dose of ramipril or placebo for 6 months. Brain tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP-9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p < 0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25% in the basal ganglia (p < 0.0001 each). No differences were observed in the amount of TIMP-1 or TIMP-2. These findings provide new insights into the biochemical mechanisms underlying extracellular matrix proliferation and its modulation by ACE inhibitors. Therapeutic alterations that influence the proteolytic systems might prove important in the prevention of extracellular matrix accumulation and secondary microvascular vessel wall changes.     

An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association.

The association of pleuropulmonary blastoma and cystic nephroma is an uncommon entity, with only 4 cases of such an association in the same patient described in English literature. We report a 5th histologically documented case in a 32-month-old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary mass showed an important regression with postbiopsy chemotherapy, allowing subsequent tumorectomy. To date very little is known about this rare entity, and a genetic link between these 2 tumors is hypothesized.     

Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1

Plasmodium falciparum may cause severe forms of malaria when excessive sequestration of infected and uninfected erythrocytes occurs in vital organs. The capacity of wild-type isolates of P falciparum-infected erythrocytes (parasitized red blood cells [pRBCs]) to bind glycosaminoglycans (GAGs) such as heparin has been identified as a marker for severe disease. Here we report that pRBCs of the parasite FCR3S1.2 and wild-type clinical isolates from Uganda adhere to heparan sulfate (HS) on endothelial cells. Binding to human umbilical vein endothelial cells (HUVECs) and to human lung endothelial cells (HLECs) was found to be inhibited by HS/heparin or enzymes that remove HS from cell surfaces. (35)S-labeled HS extracted from HUVECs bound directly to the pRBCs' membrane. Using recombinant proteins corresponding to the different domains of P falciparum erythrocyte membrane protein 1 (PfEMP1), we identified Duffy-binding-like domain-1alpha (DBL1alpha) as the ligand for HS. DBL1alpha bound in an HS-dependent way to endothelial cells and blocked the adherence of pRBCs in a dose-dependent manner. (35)S-labeled HS bound to DBL1alpha-columns and eluted as a distinct peak at 0.4 mM NaCl. (35)S-labeled chondroitin sulfate (CS) of HUVECs did not bind to PfEMP1 or to the pRBCs' membrane. Adhesion of pRBCs of FCR3S1.2 to platelet endothelial cell adhesion molecule-1 (PECAM-1)/CD31, mediated by the cysteine-rich interdomain region 1alpha (CIDR1alpha), was found be operative with, but independent of, the binding to HS. HS and the previously identified HS-like GAG on uninfected erythrocytes may act as coreceptors in endothelial and erythrocyte binding of rosetting parasites, causing excessive sequestration of both pRBCs and RBCs.     

Whole-abdomen radiation in patients with advanced ovarian carcinoma after surgery,chemotherapy and second-look laparotomy

Summary Forthy-three patients with ovarian carcinoma were treated with whole-abdomen radiation (moving strip±pelvic radiation), 15 patients had not received prior chemotherapy, and 28 patients were irradiated following chemotherapy and second-look laparotomy. Ten of these had been treated with a variety of chemotherapy regimens (L-PAM, CHAD, Hexa-CAF). Eighteen patients were treated in an ongoing prospective trial with combination chemotherapy consisting of melphalan, cis-platinum, and hexamethylmelamin (HexaPAMP). Thrombocytopenia was the limiting toxicity. A temporary pause in the radiation schedule allowing platelets to recover made it possible to complete treatment in 80% of the patients. The acute toxic effects, which included the expected side effects of radiation therapy on intestine, liver and lung, were not more frequent or more severe in the patients who had received prior chemotherapy than in those who had radiation therapy alone. Thirty-four of 43 patients (stage I, seven patients; stage II, seven patients; stage III, 27 patients; stage IV, two patients) are alive and without evidence of disease 26+ months (range 7 to 64 months) after entering the postsurgical treatment program.Paper presented at the Annual Meeting of the Swiss Society for Oncology, Basel, March 1983     

A Mirror in the Mind: A Case of Visual Allaesthesia in Homonymous Hemianopia

We report the case of a 61-year-old female patient with intracranial bleeding in left parietal and parieto-temporal regions and a history of epilepsy and migraine. MR images showed lesions of the optic radiation, but primary visual cortical areas were intact. Perimetric testing revealed an incomplete right hemianopia. The patient claimed that visual percepts from her intact field were projected as “mirror images” into the hemianopic field. The illusory images were weak and sometimes difficult to detect, but focusing spatial attention on the “mirror” image increased its saliency. Drawings the patient made of her pseudo-hallucinations revealed that the illusions were lateral transpositions instead of mirror images of real objects. The illusions were tilted in clockwise direction and were never colored, although color discrimination was unimpaired in the patient's left hemifield. We quantified the characteristics of the pseudohallucinations in several experiments: The patient was asked to adjust the position, rotation angle, and size of a white test card in her blind field so that it corresponded with the illusory projection of a card of standard size and position that was presented in the intact field. The test card was compressed in horizontal size by 20% and positioned 17° visual angle to the right of the standard, shifted 1.5° upward or downward, and rotated in clockwise direction by 22.6° on average. Large objects in the intact field were projected incompletely into the blind area. Our patient's symptoms are similar to those reported in earlier case studies of visual allaesthesia. We hypothesize that the “mirror image” is induced by sparse input from contralesional V1 via the corpus callosum upstream of the lesion site and a lack of inhibition or hyperexcitability of ipsilesional early visual areas after deafferentation. The rotation of the illusions may be induced by the parietal lesions causing faulty co-ordinate computations, e.g., an inability to integrate visual and otholitic input.     

Subjektive Qualitätskonzepte im Vergleich zu objektiven Qualitätskriterien

Background

The need for quality management in prevention and health promotion continues to grow. The role of the participants’ and course instructors’ views on quality in prevention and health promotion has been insufficiently considered. The aim of the present study was to examine the participants’ and course instructors’ views on quality in movement-related prevention and health promotion.

Methods

Four participants and four course instructors were questioned using semistructured interviews. The data were analyzed according to the structured content analysis according to Kuckartz.

Results

The views on quality of participants and course instructors were comparable. Within the participants’ and course instructors’ views on quality in movement-related prevention and health promotion the “individual relationship between therapist and patient”, “personal atmosphere”, and “class structure” were identified as important quality dimensions, while proof of effectiveness seemed to be less important. Moreover, the understanding of proof of effectiveness turned out to be inconsistent.

Conclusions

Compared to the prevention guideline of the German statutory health insurers, participants’ and course instructors’ views on quality point out the importance of process quality. In contrast, proof of effectiveness and the qualification of the course instructor play a minor role in subjective quality concepts.

     

Ramipril prevents extracellular matrix accumulation in cerebral microvessels

OBJECTIVES: The stroke-prone spontaneously hypertensive rat is a genetic model of severe hypertension with secondary vascular alterations. The aim of this study was to determine the influence of chronic hypertension and ramipril treatment on the extracellular matrix in the cerebral microvasculature. METHODS: The study consisted of three groups: six normotensive Wistar rats, six untreated spontaneously hypertensive rats, and six hypertensive rats treated with an antihypertensive dose of ramipril (1 mg kg(-1)day(-1)) for 6 months. Alterations in the extracellular matrix were examined by western blot, immunohistochemistry, and immunofluorescence using an antibody against collagen type IV. RESULTS: Western blotting showed a reduction of the total amount of collagen type IV by 50% in the ramipril group compared with the untreated hypertensive group (51.0+/-9.3% reduction, p = 0.0004). Compared with the untreated hypertensive rats, ramipril treatment prevented a loss of vessel density in the cortex (23.4+/-1.0 versus 20.4+/-2.0, p < 0.0001) and revealed a reduction of the amount of collagen per vessel (0.54+/-0.04 versus 0.60+/-0.08, p = 0.037). The ratio between the vessel wall and the lumen (0.69+/-0.08 versus 1.31+/-0.13) and the relative collagen intensity was lowered in the ramipril group (18.1+/-4.7% reduction, p < 0.0001). Using these methods the ramipril group showed similar results than the normotensive group. DISCUSSION: Ramipril treatment completely prevented these hypertensive vascular changes. These results may stimulate a therapeutic approach with angiotensin converting enzyme inhibition in human hypertensive small vessel disease.