Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.

Emerging evidence links changes in the gut microbiome and intestinal barrier function to alterations in CNS function. We examined the role of endotoxin-responsive, cAMP-specific, Pde4 subfamily b (Pde4b) enzyme in gut dysbiosis induced neuro-inflammation and white matter loss following spinal cord injury (SCI). Using a thoracic contusion model in C57Bl/6 wild type female mice, SCI led to significant shifts in the gut bacterial community including an increase in the phylum Proteobacteria, which consists of endotoxin-harboring, gram-negative bacteria. This was accompanied by increased systemic inflammatory marker, soluble CD14, along with markers of the endoplasmic reticulum stress response (ERSR) and inflammation in the SCI epicenter. Deletion of Pde4b reduced epicenter expression of markers for the ERSR and inflammation, at both acute and chronic time points post-SCI. Correspondingly, expression of oligodendrocyte mRNAs increased. Within the injury penumbra, inflammatory protein markers of activated astrocytes (GFAP), macrophage/microglia (CD11b, Iba1), and the proinflammatory mediator Cox2, were decreased in Pde4b-/- mice. The absence of Pde4b improved white matter sparing and recovery of hindlimb locomotion following injury. Importantly, SCI-induced gut dysbiosis, bacterial overgrowth and endotoxemia were also prevented in Pde4b-/- mice. Taken together, these findings indicate that PDE4B plays an important role in the development of acute and chronic inflammatory response and consequent recovery following SCI.

Randomized comparison of percutaneous Viabahn stent grafts vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral arterial occlusive disease.

OBJECTIVE: This randomized prospective study was designed to compare the effectiveness of treating superficial femoral artery occlusive disease percutaneously with expanded polytetrafluoroethylene (ePTFE)/nitinol self-expanding stent grafts vs surgical femoral-to-above knee (AK) popliteal artery bypass with synthetic graft material. METHODS: From March 2004 to May 2005, 100 limbs in 86 patients with femoral-popliteal arterial occlusive disease were identified. Patients had symptoms ranging from claudication to rest pain, with or without tissue loss, and were prospectively randomized for treatment into one of two groups. The limbs were treated percutaneously with angioplasty and one or more self-expanding stent grafts (n = 50) or surgically with femoral-to-AK popliteal artery bypass using synthetic Dacron or ePTFE grafts (n = 50). The mean +/- SD total length of artery stented was 25.6 +/- 15 cm. Follow-up evaluation with ankle-brachial indices and color flow duplex sonography imaging were performed at 3, 6, 9, and 12 months after treatment. RESULTS: Patients were monitored for a median of 18 months. No statistical difference was found in the primary patency (P = .895) or secondary patency (P = .861) between the two treatment groups. Primary patency at 3, 6, 9, and 12 months of follow-up was 84%, 82%, 75.6%, and 73.5% for the stent graft group and 90%, 81.8%, 79.7%, and 74.2% for the femoral-popliteal surgical group. Thirteen patients in the stent graft group had 14 reinterventions, and 12 reinterventions occurred in the surgical group. This resulted in secondary patency rates of 83.9% for the stent graft group and 83.7% for the surgical group at the 12-month follow-up. CONCLUSIONS: Management of femoral-popliteal arterial occlusive disease using percutaneous treatment with a stent graft is comparable with surgical revascularization with conventional femoral-to-AK popliteal artery bypass using synthetic material up to 12 months. Longer-term follow-up would be helpful in determining ongoing efficacy.

Intermediate follow-up of carotid artery stent placement.

BACKGROUND: Carotid artery stent placement (CAS) is becoming more popular among various specialties for the treatment of primary and recurrent carotid artery disease. The morbidity associated with this procedure is improving but the intermediate- and long-term follow-up remains unknown. We report our restenosis rates and follow-up associated with CAS. METHODS: Thirty-one interventions on 29 patients from May 1998 to January 2002 were reviewed. All patients have undergone serial follow-up using Doppler ultrasound at 3 and 6 months and every 6 months thereafter. Ten interventions (32%) were performed on patients with recurrent carotid artery disease and 21 (68%) on patients with primary disease. RESULTS: Five periprocedural complications occurred (transient ischemic attack, n = 3; major stroke, n = 1; immediate intrastent restenosis requiring lysis, n = 1) for a total immediate complication rate of 16%. No deaths occurred. Follow-up was achieved in all 29 patients (mean 28 months; range 20 to 46). Twenty-seven patients (29 vessels; 94%) remain asymptomatic with less than 50% stenosis. Two vessels (6%) have been found to have a critical restenosis of greater than 90%. Both patients were symptomatic from their recurrence (transient ischemic attack, n = 1; acute stroke, n = 1). Cumulative major stroke and death rate including all follow-up was 6%. CONCLUSIONS: CAS can be performed with an acceptable stroke/death rate (3%) in a properly selected patient population. In our small series of patients, the restenosis rate at a mean of 28 months after CAS is 6%.

Repair of a mycotic aneurysm of the infrarenal aorta in a patient with HIV, using a Palmaz stent and autologous femoral vein graft.

With the widespread use of endovascular surgery, aneurysms can be managed selectively with the use of stent grafts. Standard treatment of mycotic aneurysms usually requires resection and extraanatomic bypass. Although stent graft repair of a mycotic femoral aneurysm with autologous graft has been reported, we present a case of an infrarenal mycotic aneurysm in a patient with the human immunodeficiency virus (HIV) that was successfully treated with a novel endovascular approach.

Management of carotid body paragangliomas and review of a 30-year experience.

Carotid body tumors are rare neoplasms and must be considered in the evaluation of all lateral neck masses; early surgical removal has been recommended. In this study, the medical records of 29 patients with 34 carotid body paragangliomas who were treated at our institution between 1971 and 2001 were retrospectively reviewed. An overview is provided of this lesion, including diagnosis, classification, metastatic potential, possible secretory function, operative techniques, and nonsurgical methods of management. Carotid body tumors may be familial and are more often bilateral in these instances; five patients (17%) had bilateral tumors in this series. The criterion for malignancy is demonstrated by metastatic tumor in lymph nodes or distant organs. Three patients (10%) had malignant tumors, one with hepatic metastases. One patient (3%) in our series exhibited abnormal serotonin production. Vascular reconstruction was necessary in eight cases (28%). No stroke occurred, however, two arterial thromboses (7%), five permanent cranial nerve deficits (17%), and one death (3%) from massive pulmonary embolism were seen. Our experience demonstrates that early operative management is warranted to avoid the possibility of eventual metastasis and progressive local invasion to the point of inoperability.

Prospective evaluation of endoluminal venous stents in the treatment of the May-Thurner syndrome.

The May-Thurner syndrome is an acquired stenosis of the left common iliac vein causing pain, edema, or deep venous thrombosis (DVT). The patency and behavior of endoluminal venous stents for this condition was evaluated in this study. Patients with the May-Thurner lesion treated with endoluminal stenting from 1997 to 2000 were evaluated according to an institutional review board-approved protocol. Wallstents (n = 14) or Smart stents (n = 1) were placed into the left common iliac. Patency was evaluated with duplex ultrasonography using a 5 mHz linear array probe (HP 4500) at 6-month intervals. Our results showed that treatment of the May-Thurner syndrome with endoluminal stenting is associated with low morbidity and high patency rates. Longitudinal evaluation of this group of patients is ongoing to confirm these findings.