Double-paddle peroneal tissue transfer for oromandibular reconstruction

The double-paddle peroneal tissue transfer is a useful technique for reconstructing the extensive and complex defect that results after ablative surgery for oral cancer. It can facilitate the design and inset of the skin paddle and avoid the need for a second free flap. The two skin paddles can be based on either two cutaneous perforators of the peroneal vessels or two branches of a single cutaneous perforator. The authors report their experience with double-paddle peroneal tissue flaps (10 fasciocutaneous and five osteocutaneous) in 15 patients. The largest double paddle used was (16 x 9) (15 x 6) cm, and the smallest one was (7 x 5.5) (4.5 x 4) cm. All flaps were used for both intraoral and extraoral defect reconstruction. There was one single skin paddle necrosis caused by erroneous manipulation of the flap 1 week after the operation; however, the skin paddle had survived completely before the manipulation. All other flaps survived completely, with a good to excellent appearance, and no patient had a significant gait disturbance after the operation.     

Nitric oxide regulates tissue transglutaminase localization and function in the vasculature

The multifunctional enzyme tissue transglutaminase (TG2) contributes to the development and progression of several cardiovascular diseases. Extracellular rather than intracellular TG2 is enzymatically active, however, the mechanism by which it is exported out of the cell remains unknown. Nitric oxide (NO) is shown to constrain TG2 externalization in endothelial and fibroblast cells. Here, we examined the role of both exogenous and endogenous (endothelial cell-derived) NO in regulating TG2 localization in vascular cells and tissue. NO synthase inhibition in endothelial cells (ECs) using N-nitro l-arginine methyl ester (l-NAME) led to a time-dependent decrease in S-nitrosation and increase in externalization of TG2. Laminar shear stress led to decreased extracellular TG2 in ECs. S-nitrosoglutathione treatment led to decreased activity and externalization of TG2 in human aortic smooth muscle and fibroblast (IMR90) cells. Co-culture of these cells with ECs resulted in increased S-nitrosation and decreased externalization and activity of TG2, which was reversed by l-NAME. Aged Fischer 344 rats had higher tissue scaffold-associated TG2 compared to young. NO regulates intracellular versus extracellular TG2 localization in vascular cells and tissue, likely via S-nitrosation. This in part, explains increased TG2 externalization and activity in aging aorta.     

The anatomy of the extended peroneal venous system

The fibula has deservedly become a workhorse flap for vascularized bone grafts. As with most flaps, much is known regarding idiosyncrasies of its arterial supply, and the corresponding venous system has generally been assumed to be comparable. Because this donor site has become increasingly versatile, a detailed anatomic study that would verify this latter assertion should be important. Therefore, venous mapping specifically of the peroneal venae comitantes was completed in 29 fresh lower limbs. In every specimen, paired venae comitantes of large caliber indeed paralleled the course of the peroneal artery. All were of quality satisfactory for microanastomoses, which should provide reassurance that preoperative evaluation of the peroneal venous system is not routinely indicated. However, anatomic variations proved to be the norm. The two venae comitantes did not necessarily coalesce into a single common peroneal vein [6 of 29 (21 percent)]. Usually, the lateral peroneal vein was the larger and continued proximally either alone (17 percent) or as the common peroneal vein (66 percent) to form the lateral tibioperoneal vena comitans. Thus, the venous pedicle of a fibula flap could be lengthened up to its confluence with the popliteal vein, a maneuver that potentially could obviate the need for a vein graft at least on the venous side. Although anomalies of the peroneal artery could preclude use of the fibula altogether, there appeared to be no such contraindications from a venous standpoint, despite the fact that the venous anatomy was unique in every individual. Some important similarities in patterns, though, do exist. For example, a common peroneal vein was formed by the juncture of the lateral peroneal vein and some combination of branches joining the lateral posterior tibial vein and medial peroneal vein in 63 percent of all limbs. Because exceptions are the rule, the choice of donor vein and venous pedicle length best remains an intraoperative decision dependent on the presenting anatomy.     

The coronary vasculature and the myocardium

The effect of bradykinin (BK) on myocardial inotropic state was tested on 5 isolated rat heart preparations, in which a proper ballon was placed to record left ventricular pressure, whose developed systolic value was taken as an index of contractility. A reduction of developed left ventricular pressure was observed when BK was added to the perfusion oxygenated Tyrode solution. However, when BK was given after 1-amino-benzotriazole, an inhibitor of Cytochrome P-450 (Cyt P-450), developed pressure did not change. Since Cyt P-450 is known to act on arachidonic acid inducing the production of epoxiecocistrienoic acids (EETs) which hyperpolarizes myocardial fibres, it was argued that the reduction in contractility by bradykinin was the result of the hyperpolarizing effect of EETs. The fact that the concentration of Cyt P-450 is higher in the vascular endothelial cells than in the sarcolemma of the myocytes and the observation that the coronary resistance decreases together with the contractility suggest that the endothelium plays a pivotal role in mediating the negative inotropic effect of BK.     

The safety of microvascular free tissue transfer in the elderly population

The objective of this study was to evaluate the safety and thus the efficacy of microvascular free tissue transfer in the elderly patient population. Free flaps for different types of reconstructions were analyzed to verify whether free tissue transfer is feasible in the elderly. Between 1993 and 2003, 102 free flaps were performed in 94 patients who were aged 70 years or older. There were 75 male and 19 female patients, with a mean age of 73.8 years (range, 70 to 87 years). Different types of free flaps were performed for head and neck (n = 78), lower extremity (n = 12), and trunk and upper extremity (n = 4) reconstruction. Nine flaps underwent reexploration and four of them were lost, for an overall success rate of 96 percent. Medical complications in the postoperative period were further evaluated. A total of 32 medical complications were seen in 29 patients. Only one patient died because of postoperative complications. The frequency of medical complications was further analyzed in detail. Effects of American Society of Anesthesiologists status, operation time, and age on complication rate were evaluated statistically. Only American Society of Anesthesiologists status was statistically significant for the occurrence of postoperative medical complications; class III and IV patients were at higher risk than class I and II. Neither operation time nor age was predictive of postoperative complications. Microvascular free tissue transfer is a safe and reliable option in the elderly population. The success rate of free flaps is not different from that for other age groups. The rate of postoperative medical complications was 31 percent (29 of 94 patients); most complications were in American Society of Anesthesiologists class III and IV patients.     

Combined vascularized fibula and peroneal composite-flap transfer for severe heat-press injury of the forearm.

A free combined vascularized fibula and peroneal composite flap was transferred to the forearm in a patient with a severely damaged forearm following a heat-press injury. The operative technique, postoperative management, and subsequent clinical course are described, and the advantages of this method are outlined. Not only can the fibula now be used as a free vascularized bone graft in simple bone defects, but further applications, such as a combined fibula and peroneal composite flap, can be employed in the treatment of severely damaged forearms.     

Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue

There is a considerable need for cell-based in vitro skin models for studying dermatological diseases and testing cosmetic products, but current in vitro skin models lack physiological relevance compared to human skin tissue. For example, many dermatological disorders involve complex immune responses, but current skin models are not capable of recapitulating the phenomena. Previously, we reported development of a microfluidic skin chip with a vessel structure and vascular endothelial cells. In this study, we cocultured dermal fibroblasts and keratinocytes with vascular endothelial cells, human umbilical vascular endothelial cells. We verified the formation of a vascular endothelium in the presence of the dermis and epidermis layers by examining the expression of tissue-specific markers. As the vascular endothelium plays a critical role in the migration of leukocytes to inflammation sites, we incorporated leukocytes in the circulating media and attempted to mimic the migration of neutrophils in response to external stimuli. Increased secretion of cytokines and migration of neutrophils was observed when the skin chip was exposed to ultraviolet irradiation, showing that the microfluidic skin chip may be useful for studying the immune response of the human tissue.     

Gene transfer to the vasculature: historical perspective and implication for future research objectives

Cardiovascular diseases are a major cause of fatality, disability, and economic burden in Western civilization. Although the pharmaceutical industry has delivered a plethora of drugs for treatment of diverse cardiovascular complaints, there remain many conditions for which pharmacological regimens are either nonexistent or largely ineffective. In contrast, remarkable progress has been made in the field of vascular gene transfer in the last decade. The vast majority of studies are preclinical, although a number of high profile vascular gene therapy clinical trials are in progress. In principle, vascular gene therapy represents an unprecedented opportunity to treat a host of cardiovascular diseases in humans although many scientific, clinical, and ethical obstacles remain. Here we discuss the rapid progress in preclinical vascular gene therapy, highlight the most appropriate gene delivery vectors, and discuss the advances toward the ultimate goal of an efficient and safe gene therapy for diverse cardiovascular diseases.     

The lymphatic vasculature in disease

Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.     

The vasculature and limb development

The developing vascular pattern of the embryonic chick limb results from a combination of two properties: the intrinsic self-assembly and branching properties of the vascular cells and the extrinsic information associated with the expanding mitotic population of mesenchymal cells; and the inhibitory factors which restrict the entrance of vessels into particular domains and/or decrease the branching frequency of such vessels. It is hypothesized that an important component of limb pattern formation is the interplay between the dividing population of mesenchymal cells and the intrinsic properties of the vascular cells. It is further asserted that the presence of particular vascular elements may, indeed, be 'positional information'. Two examples are cited involving aspects of limb duplication to support this possibility; it is suggested that vascular vessel size of a host limb may dictate the polarity of duplication events. The presented hypothesis emphasizes that the interplay between the intrinsic properties of self-assembly into tissues and extrinsic factors which establish boundaries and morphologies is involved in both vascular and limb pattern formation.