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Nature Geoscience 5, 911–917 (2012); published online 25 November 2012. In the print version of this Article originally published, the present address for Toshitsugu Yamazaki was erroneously omitted. It is as follows: Atmosphere and Ocean Research Institute, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8564, Japan.

This study focuses on the histomorphologic damage produced by an acute elongation process, as well as on quantifying the alterations in arterial contractility following the application of this technique. Light microscopy and scanning electron microscopy studies were prepared from expanded and non-expanded pig superficial femoral arteries (SFA) harvested immediately following expansion, and again at 24- and 72-hr intervals. Histologically, the expanded vessels showed minor, patchy, endothelial slough, but not fragmentation of the internal or external elastic lamina. At 24 hr, the endothelium showed reactive changes, but no evidence of smooth-muscle necrosis of the tunica media was observed. At 72 hr, healing of the endothelium was evident by SEM. Similar specimens, also from the SFA, were harvested and placed in organ chambers immediately following expansion and 24 hr later, to measure contractility when exposed to alpha-adrenergic agonists. The vessels were exposed to the contractile agonists, phenylephrine and 5-hydroxytryptamine, which evoked similar concentration-dependent increases in tension in both the expanded group and the controls. From these observations, the authors conclude that acute intraoperative elongation of arteries results in only minor endothelial damage, without affecting the inherent contractility of the vessel wall.

This study reports four clinical cases in which acute intraoperative, extraluminal, arterial elongation was utilized. This technique was developed to facilitate end-to-end anastomoses across vascular defects traditionally bridged with vein grafts. In the reported cases, arterial defects, ranging from 17 to 25 mm, were closed primarily following the application of this technique. Follow-up, ranging from 3 to 34 months, has demonstrated patency in all cases. The authors believe this technique can be used clinically as a reliable alternative to vein grafting for the reconstruction of certain arterial defects.

This study demonstrates the feasibility of acute extraluminal expansion to elongate arteries intraoperatively in order to overcome defects too large to be repaired primarily. Twenty Sprague-Dawley rats were divided into two groups: an expander-elongation group and a nonexpanded control group of 10 rats each. Arterial resections were performed ranging from 6 to 22 mm. A miniaturized tissue expander was used to stretch vessels in three consecutive cycles over a 15- to 20-minute period (expander-elongation group). Defects twice as long as those which could be overcome by mobilization alone (nonexpanded control group) could be closed following the application of this technique without thrombosis. Initial laboratory findings and the application of this method in a clinical case are presented.

This study was designed to evaluate the feasibility of CO2 laser-assisted repair of esophageal injuries. Nine-millimeter longitudinal incisions were made in the cervical esophagus of 40 Sprague-Dawley rats. The rats were divided into two groups. Twenty rats in Group 1 had their incisions closed in two layers (mucosa and muscularis) with the I.L. Med Unilase microsurgical CO2 laser (LAREL), using 80 mW of power with a spot size of 200 mu (power density = 255). Twenty rats in Group 2 had their incisions closed in two layers using 8-0 Vicryl conventional suture technique (CST). Postoperatively, an intraluminal methylene blue injection evaluated patency and leakage. Histologic analysis was performed at 3 days, 2 weeks, 1 month, and 6 months. Patency rates of LAREL and CST were comparable. No fistulas or strictures were found with either technique. Laser-assisted repair of esophageal lacerations (LAREL) was found to be faster and easier than CST. The question arises whether small esophageal tears can be safely repaired through the endoscope. This study demonstrates the feasibility of tissue welding the esophagus. Further research is mandatory to study the applicability of this technique in the clinical setting.

Technological advances have made CO2 laser-assisted microvascular anastomoses (LAMA) feasible. This study seeks to compare results of LAMA versus CSMA (conventional suture microsurgical anastomosis) in traumatized vessels. Using a rat model, femoral arteries and veins were either crushed and transected or divided by avulsion and then repaired by either LAMA or CSMA. LAMA resulted in higher patency rates than CSMA at early postoperative observation periods. With time, the patency rates improved in both groups and, by the end of the study, the patency rates were equivalent. These findings indicate that the laser technique may be a better option when working with traumatized vessels because of the critical nature of early patency rates. The improved results may be due to a reduction of suture material at the anastomotic site when using the laser technique. Some physiologic aspects of vessel thrombosis, recanalization, and the role of collateral circulation are discussed.

The large submarine Naturaliste Plateau (NP), lying off the southwestern tip of Australia, is a poorly known part of Australia’s offshore jurisdiction. Only two dredges, one from the northern margin and one from the southern margin, have recovered rocks from this feature, which is approximately the size of Tasmania. Based on the presence of distinctive 130 m.y. old basalts at Bunbury, on the adjacent coast of Western Australia, it has been claimed that the NP may form the easternmost part of the massive Kerguelen Plateau Large Igneous Province (LIP). In this case, the NP would be underlain by thickened oceanic-type crust, and dredged rocks will provide substantial spatial and age constraints on one of the largest LIPs on Earth. However, a recent Geoscience Australia assessment suggested that much of the NP may be underlain by continental rocks. A recently completed swath mapping and dredging cruise using R/V Southern Surveyor investigated the nature and origin of the NP. Pillowed, but often highly vesicular and autobrecciated basalts were sampled along the entire length of the S margin of the NP, and at several locations on its N and NW margins. Quartz + feldspar-phyric glassy rhyolitic lavas were present in several dredges with basalts, suggesting they are part of the same igneous event. Crustal rocks, including garnet-bearing gneisses and granitic rocks, were also dredged along the S margin, including at the most westerly extent of the NP. We will present new ageand geochemical data for the extensive volcanic rocks of the Naturaliste Plateau, and evaluate possible links with the Kerguelen plume.

A simple method of performing the laser-assisted end-to-side microvascular anastomosis was devised. This technique was tested on 150 Sprague-Dawley rats in two separate series of experiments. In the first, end-to-side anastomoses were performed on the iliac artery under the normal tension due to the elastic recoil of severed vessels. Four stay sutures were placed 90 degrees apart, and the intervals were "spot welded" with a low-wattage CO2 microsurgical laser unit. The patency rate (96 percent) was equivalent to that found in a control group utilizing the conventional all-suture method (92 percent), but there was a significantly higher aneurysm rate (44 versus 11 percent). In a second model, an arterial bypass with very low anastomotic tension was performed around an obstruction created in the carotid artery. This model resulted in turbulent flow but low anastomotic tension. Here the laser-anastomosis patency rate was 98 percent, versus 42 percent for the conventional all-suture method. The placement of fewer sutures in association with turbulent flow in this model may account for the improved patency rate. The avoidance of excessive tension at the anastomotic site reduced the incidence of aneurysms to a negligible level.

Reconstruction of normal shoulder contour is possible utilizing a latissimus dorsi musculocutaneous flap at the end of a long neurovascular pedicle. The thoracodorsal vessels and their lateral divisions form the basis of the pedicle. The nerve in the pedicle is left intact if maintenance of muscle bulk is desired and sectioned if atrophy is preferred. The amount of muscle taken in conjunction with the skin island is determined by the nature of the defect to be corrected. The twin goals of a single-stage reconstruction and a satisfactory aesthetic result are achieved with this method.

An innervated cross-finger flap for treatment of severe fingertip injuries is described. With this method, the dorsal skin over the middle phalanx, together with its sensory nerve, is transferred as a compound skin-nerve flap. A neurorrhaphy is performed between this nerve and the cut end of the digital nerve at the injury site. Seven of eight patients (88 percent) treated with this method (mean follow-up time 14.4 months) achieved measurable two-point discrimination. The average for those who did was 4.8 mm. A group of patients with similar injuries treated with standard cross-finger flaps exhibited slower sensory return that progressed to a lower level. In this group (mean follow-up time 16.3 months), three of six (50 percent) achieved measurable two-point discrimination with a mean value of 9 mm.

Rat intestinal segments with intact vascular pedicles were transferred from the abdominal cavity into the subcutaneous space. After 30 days, the vascular pedicle was severed. The intestinal segments, now completely dependent on wound neovascularization, survived completely. We conclude that early survival of intestinal transfers requires perfusion through the vascular pedicle. With time in a favorable bed, new vessel ingrowth from the recipient wound into the intestinal segment provides adequate circulation so that the vascular pedicle can be safely divided with no ill effect or at most a minor mucosal slough which quickly heals. Further clinical opportunities are necessary to determine the time course for these phenomena in humans.

The effect of vitamin A on resistance to infection was evaluated. Mice treated with four consecutive daily injections of 3,000 international units of vitamin A palmitate and then challenged with either a gram-negative bacterium (Pseudomonas aeruginosa), a gram-positive bacterium (Listeria monocytogenes), or a fungus (Candida albicans), showed a significant decrease in total mortality or mortality rate compared with control animals. Five hours after challenge with P. aeruginosa, the mice treated with vitamin A had sterile blood, whereas the control animals showed persistent bacteremia until death. However, the clearance of colloidal carbon or aggregated human serum albumin by the reticuloendothelial system was unaltered by treatment with vitamin A. In addition, vitamin A did not affect in vitro growth of the three challenge organisms. These studies demonstrate that vitamin A induces nonspecific resistance to infection in mice.

For breast reconstruction the latissimus flap provides a safe and relatively simple road whose landmarks are familiar to plastic surgeons. These are reviewed. The aesthetic quality of the new breast may depend on a few key planning considerations, one of which is the flap inset site on the anterior chest wall. Theoretic and actual results of using vertical, horizontal, oblique, or curvilinear insets are examined. In many cases ignoring the old scar in favor of a fresh inferolateral curvilinear inset will provide a superior result and is to be strongly considered.

The macrophage appears to bind and present antigen to the lymphocyte in the induction and elicitation of the immune response. We have studied the nature of the interaction between dinitrophenyl-guinea pig albumin (DNA-GPA) and macrophage-rich peritoneal exudate cells (PEC) in vitro. PEC from non-immune guinea pigs are not capable of binding sufficient DNP-GPA to induce DNA synthesis in vitro by immune lymphocytes when low (10-2 µg/ml) concentrations of DNP-GPA are employed although PEC from immune animals function quite well under these conditions. At high antigen concentrations (10+2 µg/ml) PEC from both immune and non-immune animals function equally well. Incubation of non-immune macrophages in serum from immune animals causes a marked increase in the sensitivity to low antigen concentrations on the part of non-immune PEC. There is a parallel increase in the amount of DNP-GPA bound to the PEC and the degree to which these cells can stimulate immune lymphocytes to divide. This enhanced capacity of PEC to stimulate lymphocytes can be inhibited by DNP-ovalbumin (OVA), a hapten on a heterologous carrier. Also, the binding of DNP-GPA, at low concentrations, to immune PEC can be blocked by anti-immunoglobulin sera. Neither of these agents has a significant effect on the binding of DNP-GPA at high concentrations to immune macrophages or on the binding of DNP-GPA, at either low or high concentrations, to non-immune macrophages. We conclude that there are at least two mechanisms of antigen binding to the macrophage surface. One involves sites of low avidity which are effective only at relatively high antigen concentrations and which appear not to be immunoglobulin. These sites dominate at high DNP-GPA concentration for both the immune and the non-immune PEC populations. In addition, cytophilic antibody, which in hapten-carrier systems is hapten-specific and of high avidity, is present on PEC from immune animals and is the primary means by which small amounts of antigen are concentrated by immune macrophages in quantities sufficient to stimulate lymphocytes.

In the course of the immune response to a hapten-protein conjugate, 2,4-dinitrophenyl (DNP)-guinea pig albumin (GPA), a major increase in the in vitro antigen-sensitivity of peritoneal exudate lymphocyte (L) populations occurs. The predominant cell within these populations is the T lymphocyte. In addition a small percentage of macrophages are present. The response measured, antigen-stimulated DNA synthesis, reflects the response of the T lymphocytes but appears to depend upon the presentation of antigen to the T lymphocytes by macrophages. The increase in antigen sensitivity thus might either reflect an increase in the affinity for antigen of the receptors on T lymphocytes or an increase in the efficiency of macrophages in presenting antigen to T lymphocytes. That the latter is the correct interpretation is indicated by experiments involving the mixing of defined lymphocyte and macrophage populations. In these experiments it was shown that macrophages controlled the pattern of antigen sensitivity (relative responsiveness to low and high concentrations of antigen) while the lymphocytes controlled the magnitude of the response to high antigen concentrations. Furthermore, preincubation of cells from animals immunized 7 days earlier with antiserum from animals immunized 14 to 35 days earlier resulted in an increase in the sensitivity of these cells to low concentrations of antigen. This indicates that macrophage-associated cytophilic antibody determines the antigen-sensitivity of the system by allowing macrophages to bind larger amounts of antigen, when antigen is present at low concentration. This, in turn, results in more efficient stimulation of T lymphocytes. The failure to demonstrate “affinity maturation” of T lymphocyte receptors may be explained in a variety of ways but one important possibility is that there is a more limited heterogeneity in the T cells participating in this response than would be true of a comparable population of B lymphocytes.

The effects of vitamin A and hydrocortisone on the immune response have been studied in the mouse. Vitamin A treatment alone markedly increases the normal number of antibody-forming cells generated in the spleen in response to immunization with sheep red blood cells. The antibody response to immunization with dinitrophenylated ovalbumin (DNP-OVA), a hapten-protein conjugate, is also enhanced by vitamin A pretreatment. Furthermore, the immunosuppressive effect of hydrocortisone on the response to sheep red blood cells can be prevented by simultaneous administration of vitamin A.

The precise mechanisms by which immunologic tolerance is induced have not as yet been elucidated. There are a variety of different types of tolerance (1–3) and tolerance in both thymus-derived lymphocytes (T lymphocytes)2 and bone marrow-derived lymphocytes (B lymphocytes) has been described (4). Tolerance induction may involve the destruction of specific immuno-competent cells upon contact with antigen. Support for this concept comes from the finding by some investigators that the number of antigen-binding cells, which appear to be precursors of antibody-secreting cells, are reduced in tolerant animals (5, 6). One possible mechanism for tolerance induction is that antigen, upon reacting with cell surface-bound immunoglobulin receptors, may under certain conditions activate complement at the surface of the cell and thus cause destruction of these cells. Azar et al., following this line of reasoning, have produced a transient complement deficiency in mice with a variety of agents and have reported that in such temporarily complement deficient animals tolerance is more difficult to achieve than in normal animals (7–9).

A profound depression of the anti-DNP antibody response to DNP-guinea pig albumin (GPA) is induced by pretreatment of guinea pigs with the DNP conjugate of the copolymer of d-glutamic acid and d-lysine (DNP-d-GL). This tolerance is hapten-specific and previous studies have indicated that the number of precursors of anti-DNP antibody-secreting cells is diminished as a result of the tolerance induction. Thus, the tolerant state appears to be due to an immune paralysis within the precursors of antibody-secreting cells (bone marrow-derived cells). In this study, it is shown that animals tolerized with DNP-d-GL, although manifesting a marked depression in the humoral response after immunization with DNP-guinea pig albumin, display a normal delayed hypersensitivity response to DNP-guinea pig albumin. Furthermore, lymph node cells from tolerized animals incorporate thymidine into DNA when stimulated with antigen in amounts equivalent to cells from normal immune animals. Thus, cellular immune responses (thymus-derived cell mediated functions) to DNP-GPA are normal in guinea pigs pretreated with DNP-d-GL. These studies strongly reinforce the concept that a basic specificity distinction exists between receptors on precursors of antibody-secreting cells and those on cells participating in cellular immune responses.

A patient with simultaneous posterior and anterior interosseous nerve syndromes is presented. During induction of anesthesia, the paralyzed muscles exhibited denervation sensitivity to succinylcholine. Following exploration and repair of a posterior interosseous nerve defect, full function returned in the dorsal muscles as well as the flexor pollicis longus and pronator quadratus muscles.

Using an experimental model, the effect of a staged division of the pedicle of a flap on vascularization from its bed was studied. This delay procedure seemed to stimulate the ingrowth of a greater number and larger size of vessels--to enhance the blood flow from the bed with significantly greater tissue survival in the flap after complete division of the pedicle.

Our experience with the medial gastrocnemius myocutaneous flap is presented. We have found it to be a reliable flap which can be transferred in one stage to solve difficult coverage problems about the knee and upper leg.

We treated a neonate with two sites of ischemia caused by dopamine extravasation. Standard treatment called for local infiltration of phentolamine, an alpha blocker. Instead, we applied 2% topical nitroglycerin ointment and the ischemia was totally reversed.

The metabolism of glucose by rat abdominal skin flaps has been investigated at various times after flap elevation. Biopsies of flap skin taken during the first 3 days after flap elevation and incubated in vitro show a marked increase in glucose consumption and lactate production compared with normal skin. At the same time, flap tissue reserves of glucose and glycogen are lower than those of normal skin. Providing that some circulation persists, the magnitude of the changes in glucose metabolism is proportional to the degree of ischemia experienced by the flap tissue in vivo. In most cases, glucose consumption and lactate production return to normal by the end of the first week after flap elevation. These experiments thus further define a major ischemia-induced shift to anaerobic metabolism (glycolysis) that occurs in skin flaps.

To identify an anatomically reliable and functionally acceptable neurovascular free flap for use in hand reconstruction, 50 fresh cadaver feet were dissected under the operating microscope, with particular attention paid to the anatomy of the first web area. A distal communicating artery was seen in 100% of dissections, allowing either dorsal or plantar donor artery inflow to nourish the entire flap area. Because of the ease of dissection, the first dorsal metatarsal or dorsalis pedis is suggested as the donor artery, and a dorsal branch of the greater saphenous venous system is suggested as the donor vein. The deep peroneal nerve was seen to consistently innervate the first web and, along with the plantar digital nerves, is suggested as an anatomically identifiable donor nerve. Either part of the foot first web may be used alone or together as a free flap. When indicated further dorsal skin may be incorporated into the web flap to expand its application. Two-point discrimination studies of the lateral plantar surface of the great toe in 50 normal individuals showed an average of 11.2 mm. This was significantly better as a potential donor flap than the medial dorsum of the foot where the average was 32 mm. A single case demonstrating the application of this flap in hand reconstruction is presented.