Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.     

Quantitative morphology of human glioblastoma multiforme microvessels: structural basis of blood-brain barrier defect

Summary Neoplastic invasion of the brain parenchyma results in a disruption of the ultrastructure of the blood vessel walls such that serum proteins extravasate into the surrounding tissue, resulting in cerebral edema. The structural changes involved are not well understood, since the pores through which serum constituents pass (permeability routes) in normal barrier vessels and in tumor vessels where the barrier is compromised, have not been extensively explored. In this study we investigate the ultrastructure of human brain microvessels in biopsied samples of control brain tissue and five glioblastoma multiforme tumors. Electron micrographs of a total of 78 vessels were analysed with computer assisted morphometry for ultrastructural evidence of permeability routes. Fenestrations in the endothelium were not seen. Pinocytotic vesicle number and arrangement did not differ significantly from that seen in control brain vessels. Interendothelial junctions with enlarged distensions (which may represent sections through transendothelial channels) were seen in some vessels from most tumors but not in control barrier vessels. In addition, large gaps in the endothelial layer were seen in less than two percent of tumor vessels. In conclusion, glioblastoma multiforme vessels in this study show subtle alterations in vessel morphology from that seen in controls. We suggest that the high vascular permeability and resultant brain edema seen in glioblastoma multiforme tumors is likely due to the presence of channels through interendothelial junctions, and rare but large breaks in the endothelial wall.     

Short-term response of brain tissue to cerebrospinal fluid shunts in vivo and in vitro.

The purpose of the studies was to determine how gross physical characteristics of cerebrospinal fluid (CSF) shunts and the cellular proliferative response to shunts contribute to shunt obstruction. Ventricular catheters with round holes, slots, and flanges were implanted into the lateral ventricles of rabbits for 4 weeks. All shunt designs were subject to ingrowth of tissue from the ventricle wall or choroid plexus. There were no qualitative or quantitative differences between normal and hydrocephalic rabbits. Astroglial cells from newborn mice were cultured on shunt catheters for 2 or 4 weeks. The growth of these cells was poor, probably because the cells cannot attach well to the silicone rubber substrate. Contact between the shunt catheter and vascularized brain tissue is the most important factor in the genesis of shunt obstruction.     

Heparin prevents stasis-induced thrombosis through protection of the venous endothelial cells: an electron microscopic study in rabbits

This study was performed to see whether or not protection of the endothelial cells contributes to the antithrombotic effects of heparin. New Zealand albino rabbits were subjected to jugular vein stasis by single caudal ligation for 2 h. Three treatments were given: saline (control group), heparin (0.2 mg/kg) 5 or 45 min before ligature of the vein. Groups of 6-8 animals were killed at 0, 5, 15, 30 and 120 min. The following parameters were determined: (1) involution and damage of the endothelial cells by scanning and transmission electron microscopy; (2) incidence and weight of thrombi in the lumens of the veins after 2 h stasis, and (3) effects of heparin on APTT and anti-Xa activity. In the control group, stasis caused a considerable involution of the endothelial cells in the first 30 min, followed by fibrin deposition and thrombus generation. Heparin strongly reduced the damage to the endothelial cells, with very evident protection of the cell membranes, and prevented thrombus generation: there were significant decreases in both incidence and weight of thrombi. These effects of heparin were evident both shortly after (maximal anticoagulant effect) and long after (no anticoagulant effect) pretreatment. We think that, under the experimental conditions we used, heparin prevented venous thrombosis at least partially by protection of the endothelial cells, through unknown mechanisms.     

Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the neurotrophin (NT) proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. The NT-like immunoreactive structures were unevenly distributed and showed regional differences among cerebellar lobules and folia. NGF-, NT-4-, and NT-3-positive neuronal perikarya were observed in all specimens examined. At variance with the other neurotrophins, the BDNF antiserum labelled neuronal cell bodies only in newborn life and infancy, as well as extensive nerve fibre systems, whose density increased with age. The NT-antibodies, tested by Western blot on human cerebellum homogenates, revealed immunoreactive bands corresponding to proteins of heterogenous molecular weight. The results obtained provide a first demonstration of the tissue localization of the NTs in the human cerebellum from perinatal to adult age, thus suggesting their involvement in the development, differentiation and maintenance of the cerebellar connectivity. Codistribution of the four NTs or sets of them was observed in cortical and deep nuclei neurons. Multiple trophic roles for NTs, encompassing the classic target-derived and local mechanisms of support, are envisaged as significant in development, differentiation, and maintenance of the human cerebellar connectivity.     

The effect of glucocorticosteroids on the neonatal blood count

To investigate the influence of glucocorticosteroid therapy on the neonatal blood count, the haematologic data of 68 preterm and term infants, who had received a single dose of 1 mg dexamethasone i.v., were reviewed. White blood cell (WBC) count and platelet count increased after steroid therapy. The increase in WBCs was associated with an increase in the number of neutrophilic granulocytes, whereas the number of eosinophils decreased. We conclude that glucocorticosteroids after the neonatal blood count and influence its value as a diagnostic marker for bacterial infections.     

Adenosine inhibits action potential-dependent release of calcitonin gene-related peptide- and substance P-like immunoreactivities from primary afferents in rat spinal cord.

Electrical field stimulation (5 Hz) evoked a prompt outflow of calcitonin gene-related peptide- and substance P-like immunoreactivities (CGRP-LI and SP-LI, respectively) from superfused slices of the dorsal but not ventral half of the rat spinal cord. The evoked outflow was abolished by tetrodotoxin, calcium-free medium or previous exposure to capsaicin, indicating that it is produced through action potentials invading the central terminals of capsaicin-sensitive primary afferents. Adenosine as well as gamma-aminobutyric acid (GABA) or the GABAB receptor agonist (-)-baclofen produced a concentration-dependent inhibition of the evoked CGRP-LI outflow. Adenosine also inhibited the evoked SP-LI outflow. These findings demonstrate that inhibition of transmitter release from primary afferent neurons should be considered as a possible mechanism of the antinociceptive action of adenosine and adenosine analogs.