Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1.

An increase in circumferential wall tension (CWT) is an important determinant of vascular remodeling during hypertension or arteriosclerosis but also arteriogenesis. Although pivotal for such processes, the effect of this biomechanical force on venous remodeling has not yet been delineated. To this end, we raised the filling pressure in veins of the mouse auricle, which led to a 2.5-fold enlargement of these blood vessels within 4 d along with an increase in smooth muscle cell proliferation, matrix metalloproteinase 2 (MMP-2) expression and gelatinase activity. These changes were likewise observed in tissue samples of human varicose veins. Topical treatment of the auricles with a decoy oligonucleotide-neutralizing activator protein 1 (AP-1) inhibited these effects. Likewise, proliferation, MMP-2 expression, and gelatinase activity in both native and cultured venous smooth muscle cells exposed to enhanced stretch was decreased by up to 80% through inhibiting AP-1. In contrast, mutant control oligonucleotides had no effect on smooth muscle cell activation. These findings indicate that an increase in venous filling pressure and thus CWT is sufficient to activate AP-1, which, in turn, triggers varicose remodeling through fuelling MMP-2 activity and smooth muscle cell hyperplasia in the venous vessel wall.

Treatment of hemodynamic insufficiency in chronic CCA occlusion using a short saphenous vein interposition graft: diagnostic and technical considerations. An illustrative case report.

Extracranial-intracranial bypass surgery has been shown to reverse hemodynamic insufficiency on the basis of steno-occlusive disease of the internal carotid artery (ICA) or middle cerebral artery. In contrast, chronic occlusion of the common carotid artery (CCA) without extracranial donor vessels affords alternative revascularization procedures as well as a more elaborate preoperative workup. This case is intended to illustrate the specific diagnostic approach and considerations as well as a beneficial treatment modality in the setting of pronounced hemodynamic insufficiency as a consequence of a CCA occlusion, in conjunction with contralateral CCA and ICA stenoses. A 61-year-old man complaining of new onset aphasia underwent vascular imaging that revealed a proximal occlusion of the left CCA with a concomitant patent proximal ICA on ultrasound. Functional cerebral blood flow measurement including Xenon-enhanced computer tomography showed corresponding chronic hemodynamic insufficiency of the left hemisphere. The patient received a modified revascularization procedure, where a saphenous vein was used as interposition graft between the subclavian artery and the left proximal ICA. Postoperatively, both clinical and morphological improvement were noted. Successful treatment of hemodynamic insufficiency because of chronic CCA occlusion necessitates a thorough preoperative workup and application of alternative revascularization strategies.

Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma.

OBJECTIVE: Medullary thyroid carcinoma (MTC) originates from C-cells. A wide variety of tumor markers including calcitonin (CT), carcinoembryonic antigen (CEA), and chromogranin A are produced by MTC. Surgery remains the only potentially curative therapy, and early detection of the primary remains the most important prognostic factor for a positive outcome for the patient. The following case concerns a 50-year-old woman with histologically proven MTC, who completely lacked serum elevation of both CT and CEA. METHODS: We performed a total thyroidectomy with lymphadenectomy in the central compartment. Histologic sections were stained for CT, CEA, and chromogranin A. Additionally we examined the patient's blood for mutations in the RET proto-oncogene. RESULTS: Serum CT and CEA were below the detection level in the serum. The tumor showed weak staining for CT, but strong staining for CEA and chromogranin A. Sequencing of the RET-proto-oncogene revealed no mutations. Five years after the operation, the patient remains well and shows no signs of tumor recurrence. CONCLUSIONS: We hereby report of a patient with neither plasma elevation of CT nor CEA. From the clinical standpoint, it is important to determine how this subgroup of MTC should be followed because CT and CEA are of no clinical use.