Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration

Transplantation of allogeneic Schwann cells (SC) would make it feasible to reconstruct immediately peripheral nerve defects, compared to using autologous SC; however, this treatment modality has not been adequately evaluated. The aim of this study was to characterize and compare the effects of allogeneic versus syngeneic SC transplantation following peripheral nerve injury. Polyhydroxybutyrate conduits were used to bridge a 10-mm gap in the rat sciatic nerve. The conduits were filled with alginate hydrogel with or without cultured allogeneic or syngeneic genetically labeled SC, without the use of immunosuppressive therapy, and examined after 2, 3, and 6 weeks with 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase chemical staining and immunohistochemistry to quantify SC migration into the conduit, axonal regeneration, the state of SC differentiation, and the expression of major histocompatibility complexes (MHC) I and II, as well as to quantify macrophage and B- and T-lymphocyte infiltration. Allogeneic SC were rejected by 6 weeks, whereas syngeneic SC could still be identified. Allogeneic and syngeneic SC equally enhanced the axonal regeneration distance but the quantity of axons was greater using syngeneic SC. The ingrowth of SC into the conduits containing allogeneic SC was similar to that observed in the presence of syngeneic SC, indicating the absence of deleterious immune response. SC continued to express phenotypic markers of nonmyelination and these were highest in conduits with allogeneic SC. Expression of MHC I and II was higher in the conduits with allogeneic SC at 3 weeks and without significant difference in the number of macrophages and lymphocytes, except at 6 weeks, when there was a larger number of lymphocytes using syngeneic SC. In conclusion, allogeneic SC enhanced axonal regeneration distance and did not induce a deleterious immune response. In a clinical setting the immediate availability of allogeneic SC for transplantation may compensate for the better outcome achieved by the use of autologous SC that require a longer preparation time in culture.     

Corneal endothelial cell density and morphology in normal Iranian eyes

Background  

An observational case series was used to study the virulence characteristics and genotypes of paired Staphylococcus epidermidis isolates cultured from intraocular samples and from periocular environment of patients with postcataract surgery endophthalmitis.     

Corneal endothelial cell density and morphology in normal Iranian eyes

Background  

We describe corneal endothelial cell density and morphology in normal Iranian eyes and compare endothelial cell characteristics in the Iranian population with data available in the literature for American and Indian populations.     

Novel Phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416.

PURPOSE: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where "dose de-escalation" was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose. EXPERIMENTAL DESIGN: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially. RESULTS: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of >35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels. CONCLUSION: SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients.     

Neoaortic aneurysm after stage I Norwood reconstruction

Treatment of hypoplastic left heart syndrome through staged repairs has resulted in patients surviving into adulthood. Use of either aortic or pulmonary homografts in performing the neoaortic reconstruction has become the standard of practice with relatively few problems. We report the case of an asymptomatic adolescent boy who had an enlarging neoaortic aneurysm and mild neoaortic regurgitation develop after undergoing a stage I Norwood procedure using a pulmonary homograft. Given the risk for rupture and a concern for further functional deterioration of the neoaortic valve, the patient underwent repair. Histologic examination showed a striking accumulation of myxoid material as well as abnormal vasculature in both the native and engrafted portions of the neoaorta.     

Controversies in the medical clearance of recreational scuba divers: updates on asthma,diabetes mellitus,coronary artery disease,and patent foramen ovale

Primary care and sports medicine physicians are frequently consulted on medical clearance for prospective recreational divers. We discuss four common and controversial medical conditions—asthma, diabetes mellitus, coronary artery disease, and patent foramen ovale—as they relate to fitness to dive. For each condition we review the relevant anatomy and physiology, current recommendations, and the pertinent medical literature. Finally, we offer evidence-based recommendations regarding fitness to dive for potential divers with these conditions.     

Plantar forefoot pressure changes after second metatarsal neck osteotomy

BACKGROUND: The aim of this study was to evaluate plantar pressure changes after second metatarsal neck osteotomy using the Weil technique. METHODS: Six below-knee cadaver specimens were used. Each specimen was held in a custom-built apparatus and loaded to 500 N for a period of 3 seconds. Using a computerized Musgrave pedobarograph, pressure measurements were made before and after osteotomy in both neutral and 45-degree heel rise positions. All osteotomies were made at an angle of approximately 20 degrees relative to the long axis of the metatarsal shaft. The metatarsal heads were displaced proximally by 5 mm and fixed with a single Kirschner wire. RESULTS: After osteotomy there was an average decrease in pressure beneath the second metatarsal from 70.6 to 45.1 kPa in neutral and from 813.0 to 281.4 kPa in heel rise, representing statistically significant (p < or = 0.05) decreases of 36% and 65%, respectively. There also were significant decreases beneath the third metatarsal in both neutral (39%) and heel rise (37%), and beneath the fourth metatarsal in neutral position (28%). A significant pressure increase occurred beneath the first metatarsal in neutral (23%). No significant pressure changes occurred under the fifth metatarsal in either position. CONCLUSION: Overall, our results indicated that the Weil metatarsal neck osteotomy is effective at offloading the second metatarsal head at neutral and heel rise positions.     

Therapeutic advances in interventional neurology

Rapid advances in the field of interventional neurology and the development of minimally invasive techniques have resulted in a great expansion of potential therapeutic applications. We discuss therapeutic interventional neurology as applied in clinical practice in one of the two possible ways: 1) embolization leading to occlusion of blood vessels; and 2) revascularization leading to reopening of blood vessels. These procedures can be applied to a broad range of cerebrovascular diseases. In the first section of this review, we will explore the evolution of these interventions to occlude aneurysms, arteriovenous malformations, neurovascular tumors, and injuries. In the second section, revascularization in acute ischemic stroke, stenosis, and dural venous thrombosis will be discussed.     

Non-Hodgkin's lymphoma presenting as a pelvic mass with elevated CA-125

BACKGROUND: We report a case of pelvic lymphoma with an elevated serum CA-125 level, initially misdiagnosed as ovarian carcinoma. A review of the literature is presented and a possible mechanism for CA-125 elevation in diseases other than ovarian cancer is discussed. CASE: A 50-year-old woman presented with symptoms of progressive dyspnea, early satiety, fatigue, and weight loss. Workup revealed a pelvic mass and an elevated CA-125 level. Paclitaxel and carboplatin were administered to facilitate therapy and provide symptomatic relief for a presumed bulky ovarian carcinoma. A biopsy was obtained after the initiation of chemotherapy, yielding the diagnosis of diffuse large B cell non-Hodgkin's lymphoma, stage II-B. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy resulted in long-term disease remission. A search of the literature revealed several clinical series describing the elevation of CA-125 in a variety of diseases, both benign and malignant. CONCLUSIONS: In the setting of a newly diagnosed pelvic mass, care should be taken when interpreting an elevated CA-125 level. While ovarian cancer is high on the list of differential diagnoses, lymphoma cannot be excluded until a tissue diagnosis is obtained.