Sanjeev Pradhan

Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-κB, and AP-1

Investigation into the etiology of atherosclerosis has identified cigarette smoking as a major risk factor. Although it has been established that cellular adhesion molecule expression on endothelial cells is stimulated by nicotine, the mechanism by which this occurs is not clear. The aim of this study was to determine the effect of nicotine on the expression of the adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 inendothelial cells and to determine the involvement of imporcule tank known intermediaries, protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factors NF-κB and AP-1. Human umbilical vein endothelial cells (HUVEC) were exposed to 10−8M nicotine for up to 24 h. Expression of ICAM-1 and VCAM-1 and phosphorylation of p38 were examined by immunoblot. Electrophoretic mobility shift assay was performed to determine NF-κB and AP-1 activation. We observed that nicotine increased the expression of ICAM-1 and VCAM-1 with a peak at 6h.p38 MAPK was activated after 5 min exposure to 10−8 mol/L nicotine and returned to baseline levels by 30 min. Exposure of HUVEC to nicotine resulted in a 4.1-fold increase of PKC activity at 5 min, which subsequently returned to control levels by 15 min. Nicotine (10−8 mol/L) also increased NF-κB and AP-1 activity. Inhibitors of p38 MAPK, PKC, and NF-κB suppressed nicotine-stimulated expression of ICAM-1 and VCAM-1. Our results indicate that nicotine enhances the expression of ICAM-1 and VCAM-1 on the endothelial cell surface via a second messenger pathway which involves PKC and p38 MAPK-mediated activation of NF-κB and AP-1, resulting in increased expression of these cellular adhesion molecules.

Intravenous lobular capillary hemangioma originating in the iliac veins: a case report.

Intravenous lobular capillary hemangioma is a rare benign lesion that can mimic other intravascular lesions encountered by vascular surgeons, such as angiosarcoma, papillary endothelial hyperplasia, and deep vein thrombus. These lesions have been described originating in the veins of the head, neck, and upper extremities. To our knowledge, there are no reported cases of intravenous capillary hemangioma arising from within a pelvic vein. We report a case of an elderly woman found to have an extensive intravenous lobular capillary hemangioma originating in the internal iliac vein. She was successfully treated with resection, including the tumor and normal iliac vein. Diagnosis of these lesions can be difficult. We describe the utility of duplex ultrasound and magnetic resonance venography in aiding preoperative diagnosis and surgical planning. The diagnosis is ultimately confirmed with histology that demonstrates multiple capillaries lined with flattened endothelial cells grouped in a lobular fashion admixed with fibromyxoid stroma containing collagenous fibers, spindle cells, and mitotic figures. Preoperative work-up should include a duplex ultrasound and magnetic resonance venogram. Treatment should be with resection and specimen processing to rule-out malignant vascular tumors.

Urgent Carotid Endarterectomy Is Safe in Patients with Few Comorbid Medical Conditions

Recent reports from single institutions have confirmed the efficacy of carotid endarterectomy (CEA) performed in the urgent or emergent setting, although with higher perioperative mortality and morbidity. We determined the results of urgently performed CEA in academic and community hospitals and whether patient or hospital factors affected outcome. The records of patients undergoing CEA in all nonfederal hospitals in the state of Connecticut between 1992 and 2002 were reviewed, and symptomatic patients who presented in an urgent or emergent fashion were compared to patients treated electively. Multivariable logistic regression was used to determine the effect of patient risk factors on perioperative mortality, stroke, and cardiac complications. Patients undergoing urgent CEA (n = 764, 6.3%) had higher perioperative mortality (2.0% vs. 0.3%, p < 0.0001) and stroke (2.9% vs. 1.1%, p < 0.0001) but not cardiac complications (3.0% vs. 2.2%, p = 0.14) compared to patients undergoing elective CEA (n = 11,312). Patients undergoing urgent CEA and with high rates of associated comorbidity had a higher risk of perioperative mortality (7.8% vs. 0.4, p = 0.001), stroke (10.9% vs. 0.8%, p = 0.0002), and cardiac complications (14.1% vs. 0.8%, p < 0.0001) compared to patients presenting urgently but with little comorbidity. Perioperative mortality was associated with performance of the procedure in hospitals with low bed capacity (odds ratio [OR] = 4.6, p = 0.01). Perioperative stroke was associated with renal insufficiency (OR = 5.3, p = 0.04). Perioperative cardiac complications were associated with diabetes (OR = 2.6, p = 0.03) and performance in hospitals with low bed capacity (OR = 5.0, p < 0.01). Urgent admission was associated with age >/=80 (OR = 1.2, p = 0.04), renal disease (OR = 1.8, p = 0.05), and cardiac disease (OR = 1.3, p < 0.01). Urgently performed CEA has higher perioperative mortality and stroke compared with electively performed cases. However, the subset of patients with low rates of associated comorbid medical conditions but urgently needing CEA is associated with low rates of perioperative complications. Patients with severe associated comorbid medical conditions who present urgently for CEA may form a high-risk group of patients to be considered for referral to large treatment centers or possibly alternative therapy.