Application of Confocal Microscopy for 3D Assessment of Carotid Plaque Structure: Implications for Carotid Blood Flow and Stroke Research.

BACKGROUND: Little information is available on how forces resulting from fluid flow interact with structural stability of carotid atherosclerotic plaque and how such interactions may impact on stroke prevention; investigation of the 3D structure of plaque could help in such studies. The aim of this study was to investigate whether confocal microscopy can be used to obtain 3D visualization of the structure of atherosclerotic carotid plaques. METHODS: Carotid plaque specimens were collected from routine end-arterectomy surgical operations. Both bright-field microscopy and Laser Scanning Confocal Microscopy (LSCM) were used to generate 3D image data-sets and visualizations of surgically removed carotid plaques. RESULTS: Evidence of carotid plaque vulnerability was demonstrated by reduced fibrous cap thickness and large lipid-necrotic core with evidence of cracking. CONCLUSION: The generation of 3D images of carotid plaques could help in: (i) investigating key features that affect plaque structural stability; (ii) comparing 3D microstructure of the plaque with clinical imaging assessment and blood flow investigations; and (iii) developing markers to identify patients requiring clinical intervention.

Compartment syndrome: an unusual complication of influenza A infection.

This case report discusses a 43-year-old man who presented with 4-limb compartment syndrome secondary to influenza A myositis. We describe the clinical features that were present and the course of this unusual complication. We review the clinical features central to early diagnosis and treatment of compartment syndrome in order to increase awareness of this potentially life-threatening complication.

Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia.

This study evaluated the efficacy and safety of intramuscular administration of NV1FGF, a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 (FGF-1), versus placebo, in patients with critical limb ischemia (CLI). In a double-blind, randomized, placebo-controlled, European, multinational study, 125 patients in whom revascularization was not considered to be a suitable option, presenting with nonhealing ulcer(s), were randomized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1, 15, 30, and 45 (total 16 mg: 4 x 4 mg). The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25. Secondary end points included ankle brachial index (ABI), amputation, and death. There were 107 patients eligible for evaluation. Improvements in ulcer healing were similar for use of NV1FGF (19.6%) and placebo (14.3%; P = 0.514). However, the use of NV1FGF significantly reduced (by twofold) the risk of all amputations [hazard ratio (HR) 0.498; P = 0.015] and major amputations (HR 0.371; P = 0.015). Furthermore, there was a trend for reduced risk of death with the use of NV1FGF (HR 0.460; P = 0.105). The adverse event incidence was high, and similar between the groups. In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo.

Therapeutic Angiogenesis With Intramuscular NV1FGF Improves Amputation-free Survival in Patients With Critical Limb Ischemia.

This study evaluated the efficacy and safety of intramuscular administration of NV1FGF, a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 (FGF-1), versus placebo, in patients with critical limb ischemia (CLI). In a double-blind, randomized, placebo-controlled, European, multinational study, 125 patients in whom revascularization was not considered to be a suitable option, presenting with nonhealing ulcer(s), were randomized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1, 15, 30, and 45 (total 16 mg: 4 × 4 mg). The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25. Secondary end points included ankle brachial index (ABI), amputation, and death. There were 107 patients eligible for evaluation. Improvements in ulcer healing were similar for use of NV1FGF (19.6%) and placebo (14.3%; P = 0.514). However, the use of NV1FGF significantly reduced (by twofold) the risk of all amputations [hazard ratio (HR) 0.498; P = 0.015] and major amputations (HR 0.371; P = 0.015). Furthermore, there was a trend for reduced risk of death with the use of NV1FGF (HR 0.460; P = 0.105). The adverse event incidence was high, and similar between the groups. In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo.

Experimental evaluation of the effect of raised pressure in a single compartment in the lower leg on neighbouring compartments using fresh above knee amputated legs-a study of interstitial pressures with two case reports.

STUDY DESIGN: Experimental evaluation of intracompartmental pressures in a fresh above knee amputated human leg. OBJECTIVES: To determine what effect raised pressure in one compartment of the lower leg had upon its neighbour. SUMMARY OF BACKGROUND DATA: There has been no previous reports of isolated compartment pathology, following low velocity trauma, causing a compartment syndrome in all four compartments of the lower leg. METHODS: Immediately after leg amputation, the intracompartmental pressure in the deep posterior compartment was artificially raised to 100 mmHg with infused 0.9% sodium chloride solution. The resultant pressure changes in remaining compartments were recorded over 30 min. RESULTS: Five legs were evaluated. After 30 min, the mean maximum intracompartmental pressure increase found in the superficial posterior, anterior and peroneal compartments was 78.4 mmHg (range 65-94 mmHg), 25.2 mmHg (range 14-31 mmHg) and 24.8 mmHg (range 15-31 mmHg), respectively. CONCLUSIONS: This experimental data and case reports show that a compartment in which there is raised pressure may exert external pressure on a neighbouring compartment that can result in physiological changes to induce a compartment syndrome within that neighbour. The importance of assessing all compartments within a limb segment, even when associated with low velocity trauma, remains paramount.