Beating heart aortic valve replacement after previous coronary artery bypass surgery with a patent internal mammary artery graft

Re-sternotomy for aortic valve replacement (AVR) in patients with a patent internal mammary artery (IMA) graft may present a challenging surgical problem. Thus, strategies to prevent IMA graft injury include avoiding its dissection and leaving the graft open. However, when aortic cross clamping and cardioplegia are required, this approach may be associated with cardioplegia washout, suboptimal myocardial protection, and anterior myocardial wall injury. We herein describe an alternative technique for AVR on the beating heart in 4 patients with patent IMA grafts. The IMA was left unclamped and continuous retrograde coronary sinus perfusion (RCSP) was administered. Additional simultaneous antegrade venous bypass graft perfusion was established according to the extent of native coronary artery disease as well as patency and level of aortic proximal anastomoses. Using additional coronary ostia backflow control, the aortic valve was successfully replaced on the beating heart in all four cases without perivalvular leak. Postoperatively, low creatine kinase-MB fraction levels and preserved or improved ventricular function suggested very good myocardial protection. No myocardial infarction occurred in any patient. In our experience, aortic valve replacement on the beating heart using simultaneous antegrade-retrograde blood perfusion is a safe and effective method in this challenging subset of patients to prevent myocardial injury and to minimize the risk of patent IMA injury.     

Successful use of recombinant activated coagulation factor VII in a patient with massive hemoptysis from a penetrating thoracic injury

Acute massive hemoptysis is a rare complication of pulmonary injury and contusion, and it is particularly difficult to manage in the nontertiary care setting. Recombinant activated coagulation factor VII (rFVIIa) is a prothrombotic drug that is increasingly being used to treat coagulopathy in massively exsanguinating trauma patients. We report a case in which recombinant activated coagulation factor VII successfully controlled massive hemoptysis and improved ventilation from a severe pulmonary contusion in a noncoagulopathic patient who suffered a penetrating thoracic injury in a military setting in Afghanistan.     

Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood

Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life, with remission in infancy or early childhood. For approximately 50% of patients, their diabetes will relapse in later life. The majority of cases result from anomalies of the imprinted region on chromosome 6q24, and 14 patients with ATP-sensitive K+ channel (K(ATP) channel) gene mutations have been reported. We determined the 6q24 status in 97 patients with TNDM. In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). K(ATP) channel mutations were identified in 26 additional family members, 17 of whom had diabetes. Of 42 diabetic patients, 91% diagnosed before 6 months remitted, but those diagnosed after 6 months had permanent diabetes (P < 0.0001). K(ATP) channel mutations account for 89% of patients with non-6q24 TNDM and result in a discrete clinical subtype that includes biphasic diabetes that can be treated with sulfonylureas. Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes.     

Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes

Uncoupling of the endothelial nitric oxide synthase (eNOS) resulting in superoxide anion (O(2)(-)) formation instead of nitric oxide (NO) causes diabetic endothelial dysfunction. eNOS regulates mobilization and function of endothelial progenitor cells (EPCs), key regulators of vascular repair. We postulate a role of eNOS uncoupling for reduced number and function of EPC in diabetes. EPC levels in diabetic patients were significantly reduced compared with those of control subjects. EPCs from diabetic patients produced excessive O(2)(-) and showed impaired migratory capacity compared with nondiabetic control subjects. NOS inhibition with N(G)-nitro-l-arginine attenuated O(2)(-) production and normalized functional capacity of EPCs from diabetic patients. Glucose-mediated EPC dysfunction was protein kinase C dependent, associated with reduced intracellular BH(4) (tetrahydrobiopterin) concentrations, and reversible after exogenous BH(4) treatment. Activation of NADPH oxidases played an additional but minor role in glucose-mediated EPC dysfunction. In rats with streptozotocin-induced diabetes, circulating EPCs were reduced to 39 +/- 5% of controls and associated with uncoupled eNOS in bone marrow. Our results identify uncoupling of eNOS in diabetic bone marrow, glucose-treated EPCs, and EPCs from diabetic patients resulting in eNOS-mediated O(2)(-) production. Subsequent reduction of EPC levels and impairment of EPC function likely contributes to the pathogenesis of vascular disease in diabetes.     

The right vertebral artery arising as a branch of the right internal carotid artery: report of a rare case

Atypical origins of the vertebral artery (VA) are rare anatomical findings. We present an extremely rare arrangement of the cerebral circulation in a 61-year-old male patient detected on magnetic resonance angiography, where the right VA arose as a direct branch of the cervical internal carotid artery (ICA). This likely reflects the failure of the pro-atlantal artery to regress during the third to fourth week of embryological life. Although the effect of the variant on symptomology is debateable, knowledge of the potential for the VA to arise as a branch of the ICA is pertinent to radiologists and surgeons operating on the great vessels and their branches, particularly vascular surgeons undertaking carotid endarterectomy.     

Formation of a human-derived fat tissue layer in PdlLGA hollow fibre scaffolds for adipocyte tissue engineering

Development of adipose tissue-engineering strategies, where human bone marrow stromal cells (HBMSC) are combined with three-dimensional scaffolds, is likely to prove valuable for soft tissue restoration. In this study, we assessed the function of poly(dl-lactide-co-glycolide) (P_dlLGA) hollow fibres in facilitating the development of HBMSC-derived adipocytes for advancement of an associated adipocyte layer. The large surface area of 75:25 P_dlLGA fibres facilitated the rapid generation of extensive adipocyte aggregates from an undifferentiated HBMSC monolayer, where the fat-laden cells stained positive with Oil Red O and expressed the adipocyte marker, fatty acid binding protein 3 (FABP3). Following implantation subcutaneously in severely compromised immunodeficient mice, the adipogenic phenotype of the PLGA–adipocyte graft was maintained for up to 56 days. Confocal microscopy showed associated LipidTOX? Deep Red neutral lipid staining in an ^FLP_dlLGA fibre–adipocyte graft after 56 days, critical evidence demonstrating maintenance of the adipocyte phenotype in the subcutaneous graft. To support adipose tissue advancement in a defined volume, the P_dlLGA–adipocyte scaffold was encapsulated within alginate/chitosan hydrogel capsules (typical diameters, 4.0 mm). In a 28-day in vivo trial in immunodeficient mice, clusters of the capsules were maintained at the subcutaneous site. An adipocyte tissue layer advancing within the surrounding hydrogel was demonstrated.     

Tibial bone tunnel widening is reduced by polylactate/hydroxyapatite interference screws compared to metal screws after ACL reconstruction with hamstring grafts

Composite interference screws containing calcium phosphate for anterior cruciate ligament graft fixation could improve implant/bone integration and thereby reduced tunnelwidening and graft slippage. The present study investigated the effect of polylactate/hydroxyapatite interference screw (HA/PLLA) screw used for tibial graft fixation on tunnel widening and clinical outcomes compared with a metal interference screw. We hypothesized less tibial tunnelwidening with HA/PLLA screws compared to metal screws. Hundred patients with HA/PLLA screw tibial fixation was compared with 100 patients with metal screw tibial fixation. Tibial tunnel widening was measured on AP and lateral radiographs taken at 12 months follow-up. Clinical outcome was assessed by objective and subjective international Knee Documentation Committee (IKDC) scores, Noyes Sports Activity and Occupational Rating scores and KT-1000 knee laxity measurements. Tibial tunnel widening at the level of the metal screw group was 36% and 38% on AP and lateral radiographs respectively. Tunnel widening was lower in the HA/PLLA group with mean tunnel widening of 30% and 32% (p = 0.012 and 0.018) on AP and lateral radiographs respectively. No differences were found for any of the clinical scores or for anterior knee laxity. The use of a polylactate/hydroxyapatite interference screw resulted in less tibial tunnel widening than a metal screw around the screw but did not affect clinical outcome or objective knee laxity.     

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

Summary: Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.     

Rapid slowing of maximal finger movement rate: fatigue of central motor control?

Exploring the limits of the motor system can provide insights into the mechanisms underlying performance deterioration, such as force loss during fatiguing isometric muscle contraction, which has been shown to be due to both peripheral and central factors. However, the role of central factors in performance deterioration during dynamic tasks has received little attention. We studied index finger flexion/extension movement performed at maximum voluntary rate (MVR) in ten healthy subjects, measuring movement rate and amplitude over time, and performed measures of peripheral fatigue. During 20 s finger movements at MVR, there was a decline in movement rate beginning at 7–9 s and continuing until the end of the task, reaching 73% of baseline (P < 0.001), while amplitude remained unchanged. Isometric maximum voluntary contraction force and speed of single ballistic flexion and extension finger movements remained unchanged after the task, indicating a lack of peripheral fatigue. The timing of finger flexor and extensor EMG burst activity changed during the task from an alternating flexion/extension pattern to a less effective co-contraction pattern. Overall, these findings suggest a breakdown of motor control rather than failure of muscle force generation during an MVR task, and therefore that the mechanisms underlying the early decline in movement rate are central in origin.