Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy-coagulopathy.
(17/2352)
We report a case of well-documented typhoid fever in a 30-year-old woman with inactive systemic lupus erythematosus with asymptomatic lupus anticoagulant and high-titer anticardiolipin antibody (aCL). Despite prompt eradication of the Salmonella typhi obtained with appropriate antibiotic therapy, multiple organ system dysfunction occurred. The central nervous system was involved, with ischemic infarcts in the occipital lobes. High-dose corticosteroid therapy failed to improve the neurologic manifestations, which responded to repeated plasmapheresis. A sharp fall in aCL and anti-beta2-glycoprotein I antibody titers was recorded before the start of plasmapheresis. At the same time, IgM and IgG antibodies to Salmonella group O:9 lipopolysaccharide became detectable; the IgM antibodies disappeared within 4 months, whereas the IgG antibodies remained detectable during the next 13 months. Despite treatment with high-dose corticosteroids and cyclophosphamide, rapidly progressive glomerulonephritis developed, leading to chronic renal failure. There is convincing evidence of a link between the S. typhi infection and the ensuing catastrophic syndrome in this patient, probably precipitated by bacterial antigens. (+info)
Vascular endothelial growth factor attenuates leukocyte-endothelium interaction during acute endothelial dysfunction: essential role of endothelium-derived nitric oxide.
(18/2352)
Vascular endothelial growth factor (VEGF) is an endothelium-specific secreted protein that induces vasodilation and increases endothelial release of nitric oxide (NO). NO is also reported to modulate leukocyte-endothelium interaction. Therefore, we hypothesized that VEGF might inhibit leukocyte-endothelium interaction via increased release of NO from the vascular endothelium. We used intravital microscopy of the rat mesenteric microcirculation to measure leukocyte-endothelium interactions 2, 4, and 24 h after systemic administration of VEGF to the rat (120 microg/kg, i.v., bolus). Superfusion of the rat mesentery with either 0.5 U/ml thrombin or 50 microM L-NAME consistently increased the number of rolling, adhering, and transmigrated leukocytes (P<0.01 vs. control mesenteries superfused with Krebs-Henseleit buffer). At 4 and 24 h posttreatment, VEGF significantly attenuated thrombin-induced and L-NAME-induced leukocyte rolling, adherence, and transmigration in rat mesenteric venules. In addition, adherence of isolated rat PMNs to thrombin-stimulated mesenteric artery segments in vitro was significantly reduced in mesenteric arteries isolated from VEGF-treated rats (P<0.001 vs. control rats). Direct measurement of NO demonstrated a threefold increase in basal NO release from aortic tissue of rats injected with VEGF, at 4 and 24 h posttreatment (P<0. 01 vs. aortic tissue from control rats). Finally, systemic administration of VEGF to ecNOS-deficient mice failed to inhibit leukocyte-endothelium interactions observed in peri-intestinal venules. We concluded that VEGF is a potent inhibitor of leukocyte-endothelium interaction, and this effect is specifically correlated to augmentation of NO release from the vascular endothelium.--Scalia, R., Booth, G., Lefer, D. J. Vascular endothelial growth factor attenuates leukocyte-endothelium interaction during acute endothelial dysfunction: essential role of endothelium-derived nitric oxide. (+info)
Effect of locoweed (Astragalus ientiginosus) feeding of fetal lamb development.
(19/2352)
Locoweed, Astragalus lentiginosus, was fed to pregnant ewes for various periods during gestation. The principal gross effects on the developing fetuses were observed to be delayed placentation, decreased vascularization, fetal edema and hemorrhage, and alteration of cotyledon development. Deformed lambs and undersized lambs also occurred. Data from sheep fed locoweed during various periods of the entire gestation period are summarized and indicate that locoweed poisoning in the fetus as with the adult is a chronic type of intoxication. Also, poisoning of the fetus parallels poisoning in the dam. (+info)
Ultrasonographic diagnosis and color flow Doppler sonography of internal jugular venous ectasia in children.
(20/2352)
We investigated the diagnostic utility of ultrasonography in the diagnosis of internal jugular venous ectasia. Eight children (six boys, two girls) were recruited into this prospective study. Sonography of internal jugular venous ectasia in these patients revealed fusiform dilation of the internal jugular vein, and the possibility of thrombus and external compression could be ruled out. Marked variation in size of ectatic jugular veins during respiration was demonstrated under real-time sonography. The mean anteroposterior diameter of these dilated internal jugular veins was 0.79+/-0.18 mm (mean+/-standard deviation), which increased to 1.58+/-0.27 mm with Valsalva maneuver. Our study showed that the anteroposterior diameters of the internal jugular veins in cases of ectasia were greater than those of contralateral jugular veins in same patients as well as those in normal children, and they showed greater increase after Valsalva maneuver. Under color Doppler flow studies, turbulent vascular flows were demonstrated in these patients with jugular venous ectasia. No progression of venous ectasia was found in any of our patients during a 6 month follow-up period. We conclude that internal jugular venous ectasia in children is a benign condition, which usually does not require surgical intervention. Ultrasonography is a good diagnostic modality for the diagnosis of internal jugular venous ectasia. Color Doppler ultrasonography demonstrate the turbulent flow in jugular venous ectasia. (+info)
Nitric oxide modulation of focal adhesions in endothelial cells.
(21/2352)
A permissive role of nitric oxide (NO) in endothelial cell migration and angiogenesis promoted by vascular endothelial growth factor (VEGF), endothelin, and substance P has previously been established. The present studies were designed to examine the mechanism(s) involved in the NO effect on focal adhesions. Time-lapse videomicroscopy of human umbilical vein endothelial cells (HUVECs) plated on the silicone rubber substrate revealed that unstimulated cells were constantly remodeling the wrinkling pattern, indicative of changing tractional forces. Application of NO donors reversibly decreased the degree of wrinkling, consistent with the release of tractional forces exerted by focal adhesions and stress fibers. Morphometric and immunocytochemical analyses showed that NO inhibited adhesion and spreading of HUVECs and attenuated recruitment of paxillin to focal adhesions. NO also had a profound dose-dependent effect on the formation of stress fibers by HUVECs. De novo formation of focal adhesions in HUVECs was significantly diminished in the presence of NO donors. Migration of HUVECs showed an absolute requirement for the functional NO synthase. NO donors did not interfere with focal adhesion kinase recruitment to focal adhesions but affected the state of its tyrosine phosphorylation, as judged from the results of immunoprecipitation and immunoblotting experiments. Videomicroscopy of HUVECs presented with VEGF in a micropipette showed that the rate of cell migration was slowed down by NO synthase inhibition as well as by inhibition of tyrosine phosphorylation. Collectively, these data indicate that NO reversibly releases tractional forces exerted by spreading endothelial cells via interference with the de novo formation of focal adhesions, tyrosine phosphorylation of components of focal adhesion complexes, and assembly of stress fibers. (+info)
Allelic and locus heterogeneity in inherited venous malformations.
(22/2352)
Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations. (+info)
In vivo microscopic study of microcirculatory perfusion of the skin of the foot in peripheral vascular disease.
(23/2352)
OBJECTIVES: the aim of this study was to determine the proportion of perfused capillaries in the skin of the foot in patients with peripheral vascular disease, and compare it with that in normal subjects. DESIGN: experimental study comparing capillary perfusion in nine patients with severe peripheral vascular disease (group 2) with seven age- and sex-matched control subjects (group 1). MATERIALS AND METHODS: using in vivo video microscopy, a method was developed to measure the ratio of perfused to total capillaries, by comparing the numbers of corresponding capillaries before and after intravenous injection of sodium fluorescein. RESULTS: the mean percentage ratio of perfused to total capillaries was 54.7% (range 41-87%, standard deviation 16.5) in group 1, and 86.0% (range 62-100%, standard deviation 13.2) in group 2 (p<0.001, t-test). CONCLUSION: a significantly higher proportion of capillaries is perfused in the skin of the foot of patients with severe peripheral vascular disease than in that of normal subjects. This is of important pathophysiological significance and may have clinical implications with regard to the role of pharmacological intervention in severe limb ischaemia. (+info)
Phlebosclerosis of the colon with positive anti-centromere antibody.
(24/2352)
A 56-year-old woman with symptoms of chronic bowel disease presented a peculiar calcification of the mesenteric vein of the ascending to transverse colon on barium enema study. The resected colon was hard and black. Histo-pathologic examinations demonstrated fibrous change of the colon with a calcified and hyaline-deposited mesenteric vein. No cell infiltration was observed. These findings were compatible with phlebosclerosis and also with systemic sclerosis. Positive anti-centromere antibody and Raynaud's phenomenon, hallmarks of a variant systemic sclerosis, the CREST syndrome were observed. We therefore speculated that the pathogenesis of the phlebosclerosis of the colon is related to the CREST syndrome. (+info)