Intra-arterial administration of cell-based biological agents for ischemic stroke therapy

Introduction: Ischemic stroke is becoming a primary cause of disability and death worldwide. To date, therapeutic options remain limited focusing on mechanical thrombolysis or administration of thrombolytic agents. However, these therapies do not promote neuroprotection and neuro-restoration of the ischemic area of the brain.

Areas covered: This review highlights the option of minimal invasive, intra-arterial, administration of biological agents for stroke therapy. The authors provide an update of all available studies, discuss issues that influence outcomes and describe future perspectives which aim to improve clinical outcomes. New therapeutic options based on cellular and molecular interactions following an ischemic brain event, will be highlighted.

Expert opinion: Intra-arterial administration of biological agents during trans-catheter thrombolysis or thrombectomy could limit neuronal cell death and facilitate regeneration or neurogenesis following ischemic brain injury. Despite the initial progress, further meticulous studies are needed in order to establish the clinical use of stem cell-induced neuroprotection and neuroregeneration.     

Leadership Development in UK Medical Training: Pedagogical Theory and Practice

Phenomenon: The central role of clinical leadership in achieving the vision of quality and productivity could be attained by investing in its development in postgraduate medical education. Approach: A critical review of selected literature is presented. Findings: The author identifies some of the main theoretical constructs related to leadership; the pedagogical underpinning of medical leadership programs; their learning objectives; and the mixture of methods, individual and collective, to achieve them. Insights: How to best develop leadership through medical education remains an open debate. Experiential learning, reflective practice, action learning, and mentoring could provide the foundations of leadership development. Application of the aforementioned should be cautious due to limitations of the concept of leadership as currently promoted and lack of robust evaluation methodologies.     

Soluble transferrin receptors and tissue oxygenation in non anaemic cystic fibrosis patients.

BACKGROUND: Chronic pulmonary disease and progressive tissue hypoxia are major causes of morbidity and mortality in cystic fibrosis (CF). Normally the body adapts to tissue hypoxia by increasing the red cell mass and decreasing the Hb-O(2) affinity. These adaptations are commonly observed in patients with cyanotic heart disease and individuals living at high altitude. However, patients with CF not only have an impaired erythroid response to hypoxia, but also are frequently anaemic. METHODS: In order to evaluate erythroid marrow activity and tissue oxygenation in 37 patients with CF we measured: the haematological and blood chemistry parameters; including red cell indices, ferritin, erythropoietin (Epo) and soluble transferrin receptors (sTfR) levels; arterial blood gases, P(50) and oxygen release to the tissues (O(2)(R)) and the 2,3-BPG levels. RESULTS: The main results showed that a) patients with CF have a mild degree of tissue hypoxia which is expressed by the moderately decreased of P(50) and O(2)(R) values and the relative increase of Epo level, b) 2,3-BPG synthesis in patients with CF is normal and c) sTfR levels are significantly increased (3-fold normal) in patients with CF compared to normal controls. CONCLUSIONS: The above observations indicate that erythroid marrow activity in patients with CF is increased.     

Dental Arch and Cephalometric Changes Following Treatment for Class III Malocclusion by Means of the Function Regulator (FR-3) Appliance

AIM: The aim of this retrospective clinical study was to evaluate dental arch, skeletal, dentoalveolar, and soft tissue profile changes following treatment of Class III malocclusion by means of the Function Regulator (FR-3) appliance. SUBJECTS AND METHODS: The study sample consisted of 14 growing patients (seven boys and seven girls) with a mean age of 9.7 +/- 1.1 years presenting Class III malocclusion. They were treated with an FR-3 appliance exclusively for a period of 2.4 +/- 0.6 years. Dental casts and lateral cephalometric radiographs were obtained immediately before initiation and after completion of treatment with the FR-3 appliance. Thirteen variables were used for the dental cast analysis and 61 variables for the cephalometric analysis. The paired t-test was utilized to evaluate the presence of significant changes (p < 0.05). RESULTS: The evaluation of the dental casts revealed that there was a significant increase in intermolar, interpremolar, and intercanine width of the maxilla and of palatal height after treatment. Concerning the mandible, an increase in intermolar and intercanine width and a decrease in lower arch depth were observed. Cephalometric evaluation revealed a significant decrease in SNB angle and an increase in ANB angle, overjet, facial convexity, nose prominence, and lower soft tissue face height. There was an increase in upper lip thickness and a decrease in lower lip convexity observed after treatment. CONCLUSIONS: The results of this study confirm a favorable functional and esthetic maxillary and mandibular position following treatment by means of the function regulator (FR-3) appliance.     

Accuracy of single-time, multilevel registration in image-guided spinal surgery.

BACKGROUND CONTEXT: Computerized frameless stereotactic image-guidance has been used in recent years to improve the accuracy and safety of pedicle screw placement during spine surgery. Because the possibility of intervertebral motion exists, and because the patient is usually in a different position when preoperative imaging is performed compared with the operative position, it has been suggested that the imaging model of the complete lumbar spine and the surgically exposed lumbar spine may be significantly discordant. Consequently, current protocols suggest registering each spinal level (single-level registration) separately before pedicle screw placement at that level, a time-consuming process. PURPOSE: To assess the accuracy of single-time multilevel registration for multilevel pedicle screw placement during image-guided, computer-assisted spine surgery, in the setting of degenerative disorders of the lumbar spine. STUDY DESIGN/SETTING: This is a prospective clinical and radiological study of 45 patients with degenerative disorders of the lumbar spine who underwent instrumented fusion with the use of single-time multilevel registration computer-assisted, image-guided tomography. The accuracy of the pedicle screws placement was confirmed on the basis of a protocol that included intraoperative spontaneous electromyographic (EMG) recordings, direct pedicle visualization, and computer tomography (CT) scans when clinically indicated during the follow-up period. PATIENT SAMPLE: Forty-five consecutive patients who fulfilled the criteria of computer-assisted, image-guided tomography pedicle screw placement for degenerative lumbar spine disease without overt instability. OUTCOME MEASURES: The principal outcome measure was the accuracy of pedicle screw placement with single-time multilevel registration for multilevel pedicle screw placement during image-guided, computer-assisted spine surgery; postoperative CT performed for clinical indications during the follow-up course was used for the assessment of pedicle screw placement. METHODS: Patients were assessed clinically before and after the operation. Data from 45 consecutive cases of image-guided, computer-assisted lumbar spinal fusion were statistically analyzed to determine the relationship between the number of levels registered during single-time registry and the mean registration error (MRE). Intraoperative spontaneous EMG, direct visualization, and postoperative CT scans were used to assess the accuracy of pedicle screw insertion. RESULTS: None of the patients involved in this study experienced clinical sequelae of improper pedicle screw placement. MREs after surface mapping and after point merge were small (less than 1.00 mm and less than 3.00 mm, respectively). During the intraoperative assessment of the pedicle screws placement, no significant spontaneous EMG activity was recorded and the pedicular walls were found intact in direct visualization. The postoperative CT scans showed in 10 patients accurate placement in 55 of the 57 pedicle screws with expansion of the medial wall in two screws. CONCLUSIONS: Single-time, multilevel registration may decrease operative time relative to repeated, single-level registrations, without compromising the increased accuracy of pedicle screw placement afforded by this technique in the setting of degenerative disorders of the lumbar spine. Despite the advantages in computer-guided image surgery, cautious application in the individual patient is recommended until more comprehensive data can be gathered in specific degenerative pathology with overt instability; thus the knowledge of the anatomy remains crucial.     

Antegrade interlocking nailing of humeral shaft fractures

The results of 39 humeral shaft fractures (37 patients) treated with antegrade locked nailing using a Russell–Taylor nail were reviewed. There were 30 acute fractures, 6 fractures malaligned in a hanging cast or brace, and 3 pathological fractures. Patient age ranged from 26 to 80 years (average, 59.7 years) and average follow-up was 25.7 months (range, 6–48 months). Fracture union was achieved in 92.3% of our cases, while shoulder function was excellent or good in 87.2% of cases. Antegrade locked nailing offers a dependable solution for the treatment of humeral shaft fractures, especially in polytrauma patients and cases of segmental or pathological fractures. Far less satisfactory results were obtained in comminuted fractures of the proximal third in the humerus, especially in osteoporotic patients, and we therefore advocate caution with the use of intramedullary nailing in this type of fracture. Certain technical aspects such as avoiding nailing the fracture in distraction, properly countersinking the tip of the nail, and achieving adequate fixation stability have been found to be of paramount importance to reduce the incidence of delayed union/non-union rate and to obtain better functional results from the shoulder joint.     

Quantifying osteoblast and osteocyte apoptosis: challenges and rewards.

Since the initial demonstration of the phenomenon in murine and human bone sections approximately 10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo-long terminal illness in the life of a 75-yr-old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls.