Late ultrastructural changes in the retina of the rat following low-dose X-irradiation

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3–12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glia1 cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.     

Ankle-brachial index and extent of atherothrombosis in 8891 patients with or at risk of vascular disease: results of the international AGATHA study.

AIMS: AGATHA (a Global Atherothrombosis Assessment) was designed to assess the extent of atherothrombosis and the use of the ankle-brachial index (ABI) in vascular patients. The principal hypotheses were that (1) in diseased patients, a low ABI was related to the number and site of vascular beds affected and (2) in at-risk patients without disease, a low ABI was related to the number of risk factors present. METHODS AND RESULTS: Patients were recruited consecutively by 482 clinicians in 24 countries and the ABI measurement was performed at a single visit. Of 8891 patients recruited, 1792 were defined as at risk and 7099 as with disease. Of the with-disease patients, 65.2% had one arterial bed affected, 27.6% two and 7.1% all three. Abnormal ABI (< or =0.9) was present in 30.9% of at-risk and 40.5% of with-disease patients. A lower ABI was weakly associated with an increasing number of risk factors in at-risk patients (r=-0.056, P=0.02) and with the site and number of arterial beds affected in with-disease patients (P<0.001). CONCLUSION: This large international study confirms that atherothrombotic disease often occurs at more than one site. The ABI is related to the risk factor profile and to the site and extent of atherothrombosis.     

Virtual real-time digital processing of hemodynamic data

At present, the majority of cardiac catheterization laboratories acquire and store hemo-dynamic data in analog form. To examine the possibility of performing complex analysis of digital data during the catheterization procedure, we examined whether virtual realtime digital (fast Fourier) analysis improves the accuracy of clinical data. We compared digital filtering of fluid manometry during right heart catheterization with 10-Hz and 250-Hz analog filters. Using the simultaneously acquired micromanometry as the “gold standard,” we found that analog filtering is associated with a greater error and time delay than digital filtering. This study demonstrates that digital hemodynamic data analysis performed during cardiac catheterization can improve the quality of data obtained during right heart catheterization, with the results available within seconds. More extensive use of computers in the cardiac catheterization laboratory may be useful for both clinical and research purposes. © 1992 Wiley-Liss, Inc.     

Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Structure function interface with sequential shortening of basal and apical components of the myocardial band

Objective: To mechanically test the intact cardiac structure to determine the sequence of contraction within the myocardial mass to try to explain ejection and suction. Methods: In 24 pigs (30–85 kg), segment shortening at the site of sonomicrometer crystals was continuously recorded. The ECG evaluated rhythm, and Millar pressure transducers measured intraventricular pressure and dP/dt. Results: Study of segment shortening defined a sequence of contraction within the myocardial mass, starting at the free wall of the right ventricle and on the endocardial side of the antero-septal wall of the left. Crystal location defined underlying contractile trajectory; transverse in right ventricle followed by basal posterior left ventricle, and from the endocardial anterior wall to the posterior apical segment and finally to the epicardial side of the anterior wall. Mean shortening fraction averaged 18±3%, with endocardial exceeding epicardial shortening by 5±1%. Epicardial segment crystal displacement followed endocardial shortening by 82±23 ms in the anterior wall, and finished 92±33 ms after endocardial shortening stopped, time frame that matches the interval of fast drop of ventricular pressure and the start of suction. Conclusions: Crystal shortening fraction sequence followed the rope-like myocardial band model to contradict traditional thinking, with two starting points of excitation–contraction, the right anterior free wall of the right ventricle, and the endocardial side of the anterior wall. Active suction may be due to active shortening of the epicardial fibers of the anterior wall, because relaxation was not detected when both mitral and aortic valves were closed during the interval previously termed ‘isovolumetric relaxation’.     

Chronische Diarrh?en unter NSAR

Ohne Zusammenfassung