Preoperative two-dimensional echocardiographic prediction of prosthetic aortic and mitral valve size in children

Preoperative two-dimensional echocardiograms (2D-ECHOs) were done on 18 patients to determine the accuracy of assessing the mitral and aortic anulus diameter in children undergoing valve replacement. Fourteen patients underwent primary valve replacement and four underwent repeat valve replacement. The mean age was 11.5 years (range 2 to 17 years). The 2D-ECHO measured mitral or aortic valve anulus was compared with the external diameter of the largest prosthetic valve that could be inserted. There was a strong correlation (r = 0.99, p less than 0.001, SEE = 1.0 mm) between the 2D-ECHO measurements and the prosthetic valve size in patients undergoing primary valve replacement, but the correlation (r = 0.16, p = NS) was poor for those undergoing repeat valve replacement. In conclusion, 2D-ECHO prediction of prosthetic mitral and aortic valve size is accurate in children undergoing primary valve replacement but is poor in those undergoing repeat valve replacement.     

α-Galactosylceramide Promotes Killing of Listeria monocytogenes within the Macrophage Phagosome through Invariant NKT-Cell Activation

α-Galactosylceramide (α-GalCer) has been exploited for the treatment of microbial infections. Although amelioration of infection by α-GalCer involves invariant natural killer T (iNKT)-cell activation, it remains to be determined whether macrophages (Mφ) participate in the control of microbial pathogens. In the present study, we examined the participation of Mφ in immune intervention in infection by α-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal Mφ from C57BL/6 mice, but not iNKT cell-deficient mice, were enhanced after intraperitoneal injection of α-GalCer despite the absence of iNKT cells in the peritoneal cavity. High levels of gamma interferon (IFN-γ) and nitric oxide (NO) were detected in the peritoneal cavities of mice treated with α-GalCer and in culture supernatants of peritoneal Mφ from mice treated with α-GalCer, respectively. Although enhanced bactericidal activity of peritoneal Mφ by α-GalCer was abrogated by endogenous IFN-γ neutralization, this was only marginally affected by NO inhibition. Similar results were obtained by using a listeriolysin O-deficient strain of Listeria monocytogenes. Moreover, respiratory burst in Mφ was increased after α-GalCer treatment. Our results suggest that amelioration of listeriosis by α-GalCer is, in part, caused by enhanced killing of L. monocytogenes within phagosomes of Mφ activated by IFN-γ from iNKT cells residing in an organ(s) other than the peritoneal cavity.Listeria monocytogenes, a Gram-positive facultative intracellular bacterium, is the causative agent of listeriosis, with an overall mortality rate of 30% (76). A major virulence factor of L. monocytogenes is listeriolysin O (LLO), a 58-kDa protein encoded by the hly gene (26, 42, 65). LLO promotes intracellular survival of L. monocytogenes in professional phagocytes such as macrophages (Mφ) by promoting listerial escape from the phagosome into the cytosol (10, 22, 26, 42, 62, 65). Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes infection and among these, mononuclear phagocytes are critical (56, 61). Activation of Mφ by gamma interferon (IFN-γ) is mandatory for elimination of L. monocytogenes (31, 35). Nitric oxide (NO) synthesized by inducible NO synthase, which is localized in the cytosol of professional phagocytes, participates in killing of L. monocytogenes (48, 52, 69, 71). Similarly, reactive oxygen intermediates (ROI) play a role in killing of L. monocytogenes within the phagosome (52, 53, 59).Natural killer T (NKT) cells represent a unique T-lymphocyte population expressing NKR-P1B/C (NK1.1; CD161), which is a type 2 membrane glycoprotein of the C-type lectin superfamily (6). In the mouse, the majority of NKT cells express an invariant T-cell receptor (TCR) α chain encoded by Vα14/Jα18 gene segments and a TCRVβ highly biased toward Vβ8.2, Vβ7, and Vβ2 (invariant NKT [iNKT] cells) (6). In contrast to conventional T cells, which recognize antigenic peptides presented by polymorphic major histocompatibility complex class I or class II molecules, iNKT cells recognize glycolipid antigens, including α-galactosylceramide (α-GalCer), a synthetic glycolipid originally isolated from a marine sponge, presented by the nonpolymorphic antigen presentation molecule CD1d (6, 40). iNKT cells are highly versatile and promptly produce both type 1 and type 2 cytokines, such as IFN-γ and interleukin-4 (IL-4), respectively, upon activation through their TCRs (1, 15-17, 79). IL-15 is an essential growth factor of both iNKT cells and NK cells and, hence, both cell populations are absent in IL-15-deficient (IL-15^−/−) mice (58). The numbers of iNKT cells are also markedly reduced in SJL mice because of a large deletion in their TCRVβ genetic region (5, 78).In vivo administration of α-GalCer causes prompt release of various cytokines by iNKT cells, which are involved in the control of various diseases, e.g., tumor rejection and prevention of autoimmune diseases (33, 41, 67, 70). Although α-GalCer has been reported to enhance host resistance to some microbial pathogens (27-29, 37, 39, 44, 55, 64), its potential role in protection against intracellular bacterial infections remains enigmatic.We have recently described that α-GalCer ameliorates murine listeriosis, which is, in part, caused by accelerated infiltration of inflammatory cells into the liver (18), although iNKT cells themselves exacerbate disease (19). Because Mφ play a central role in the elimination of L. monocytogenes, we considered the possibility that Mφ participate in enhanced resistance to L. monocytogenes infection caused by α-GalCer treatment. In the present study, we examined the influence of α-GalCer on listericidal activities of Mφ using a virulent and an avirulent strain of L. monocytogenes.     

Effect of viscous macromolecules on peritoneal plasminogen activator activity: a potential mechanism for their ability to reduce postoperative adhesion formation

Activity of peritoneal plasminogen activator and its regulation by dextran and other macromolecules that clinically suppress postoperative adhesions was studied. Plasminogen activator activity was assayed by a two-stage globinolytic assay that monitors formation of plasmin, as well as by cleavage of a chromogenic peptide substrate (S-2444) in the presence of aprotinin (Trasylol). Plasminogen activator activity was located on the outer surface of human peritoneum. Incubation of peritoneal tissue with buffer in vitro (conditioning) prompted release of plasminogen activator into the conditioning medium. The released plasminogen activator formed a single band on sodium dodecyl sulfate-gel electrophoresis at an apparent molecular weight of 174,000 and was markedly suppressed by antiserum raised against human melanoma tissue-type plasminogen activator. Nonspecific proteolytic activity did not accumulate in the medium during conditioning. The presence of dextran 80 during conditioning of peritoneum reversibly suppressed tissue-bound plasminogen activator activity and reduced plasminogen activator activity in the spent medium. A similar inhibition of peritoneal plasminogen activator was induced by dextran 500, methyl cellulose, and polyvinylpyrrolidone. Dextran, when added to the medium after conditioning, had no direct inhibitory effect on plasminogen activator activity. Dextran did not induce peritoneal production of inhibitor(s) of trypsin, chymotrypsin, or urokinase. On the basis of these findings, two possible mechanisms for the effect of viscous polymers in the reduction of adhesion formation are proposed. These mechanisms consider the importance of peritoneal tissue-type plasminogen activator for removal of fibrin clots and suggest that polymer coating either prevents the shedding of plasminogen activator into the abdominal cavity or reduces the access of fibrin clots to the serosal surfaces.     

Resection of advanced stage neuroblastoma with the cavitron ultrasonic surgical aspirator

Current protocols for the treatment of neuroblastoma emphasize total or near total resection of tumor to improve survival. This is preferentially performed as a primary procedure, or is attempted at a second-look operation. Unfortunately, this tumor often grows to large size with invasion of the spinal canal, or encasement of major vascular or other retroperitoneal structures. A primary attempt at complete removal may result in difficult-to-control hemorrhage or injury to, or loss of, vital organs. A second-look procedure carries other intrinsic risks. It often must be performed during a period of chemotherapeutically induced hematologic and immunologic suppression. The presence of adhesions and dense scar tissue increases the complexity of the dissection. The Cavitron Ultrasonic Surgical Aspirator (CUSA) combines continuous fragmentation, irrigation, and aspiration in one instrument. Tissues high in water content are selectively fragmented and aspirated, while tissues high in collagen and elastin (such as blood vessels and pseudocapsular walls) are selectively spared. Five patients, two with large pelvic dumbell tumors, two with large intrathoracic tumors, and one with a seemingly unresectable large right adrenal tumor (crossing the midline with extensive aortocaval nodal involvement) had total or near-total resection accomplished using the CUSA. In these patients, initial resection of the relatively soft inner part of the tumor left a collapsed pseudocapsule, which was then removed under greatly improved exposure in a relatively small field. The constant aspiration virtually eliminated tumor spillage. Since most vessels were skeletonized without penetration, total blood loss was minimized. There were no intraoperative or postoperative complications.     

Successful reconstruction of natural femoral anteversion using a short femoral stem in total hip arthroplasty surgery

ObjectiveTotal hip arthroplasty (THA) involves postoperative risks, such as thigh pain, periprosthetic fractures, and stress yielding. Short, anatomical, metaphyseal-fitting, cementless femoral stems were developed to reduce these postoperative risks. This study aimed to examine the “MiniMAX” prosthesis, which is a new generation, short, anatomical femoral stem made by Medacta.MethodsPatients underwent a low-dose computed tomography scan. Femoral anteversion was measured. We assessed the position and anteversion of the femoral component and compared them with the unoperated side. We also assessed the patients’ satisfaction and functional levels at 6 months postsurgery using the Harris Hip Score (HHS) and the Oxford Hip Score (OHS).ResultsNineteen individuals were recruited in this study. We found no significant difference in femoral anteversion between the operated hip and the native hip. Using the HHS and OHS questionnaires, we found clinical improvement in the 6-month postoperative scores compared with the preoperative scores.DiscussionThe new-generation, short, anatomical femoral stem made by Medacta is successful in reproducing natural femoral anteversion, while also improving patients’ functioning and lifestyle. Future large-scale, prospective comparison trials are required to further investigate this topic.     

Lidocaine injections targeting CA3 hippocampus impair long‐term spatial memory and prevent learning‐induced mossy fiber remodeling

Learning a spatial location induces remodeling of the mossy fiber terminal field (MFTF) in the CA3 subfield of the dorsal hippocampus (Ramirez‐Amaya et al. ( 2001 ) J Neurosci 21:7340–7348; Holahan et al. ( 2006 ) Hippocampus 16:560–570; Rekart et al. ( 2007a ) Learn Mem 14:416–421). These fibers appear to grow from the stratum lucidum into distal stratum oriens. Is this axonal growth dependent on “repeated and persistent” neural activity in the CA3 region during training? To address this issue, we targeted local inactivation of the MFTF region in a post‐training, consolidation paradigm. Male Wistar rats, bilaterally implanted with chronic indwelling cannulae aimed at the MFTF CA3 region, were trained on a hidden platform water maze task (10 trials per day for 5 days). Immediately after the 10th trial on each training day, rats were injected with lidocaine (4% w/v; 171 mM; n =7) or phosphate‐buffered saline (PBS; n = 7). Behavioral measures of latency, path length, and thigmotaxis were recorded, as was directional heading. A retention test (probe trial) was given 7 days after the last training day, and brains were subsequently processed for MFTF distribution (Timm's stain) and cannula location. Lidocaine treatment was found to block the learning‐associated structural remodeling of the MFTF that was reported previously and observed in the PBS‐injected controls. During training, the lidocaine group showed elevated latencies and a misdirected heading to locate the platform on the first trial of each training day. On the 7‐day retention probe trial, the lidocaine‐injected group showed poor retention indicated by the absence of a search bias in the area where the platform had been located during training. These data suggest that the reduction of neuronal activity in the CA3 region impairs long‐term storage of spatial information. As this was associated with reduced MFTF structural remodeling, it provides initial anatomical and behavioral evidence for an activity—dependent, presynaptic growth model of memory. © 2010 Wiley‐Liss, Inc.