Comparison of radial forearm with fibula and scapula osteocutaneous free flaps for oromandibular reconstruction

OBJECTIVE: To compare our experience with the osteocutaneous radial forearm free flap (group 1) (n = 108) with other commonly used osteocutaneous free flaps (group 2) (n = 56) such as the fibula and scapula in single-stage oromandibular reconstruction. DESIGN: Retrospective case review. SETTING: Tertiary-care academic medical center. PATIENTS: One hundred sixty-three consecutive patients who underwent 164 mandibular reconstructions with osteocutaneous free flaps. MAIN OUTCOME MEASURES: Assessment of preoperative and intraoperative variables for both groups. We compared recipient-site complication rate, intensive care unit stay, total hospital stay, and postoperative function. RESULTS: The most common donor site used was the radius (n = 108 [66%]), followed by the fibula (n = 36 [22%]) and scapula (n = 20 [12%]). Mean follow-up was 29 months (range, 1-116 months). Group 2 patients had larger soft tissue and/or bony defects. Surgical and medical complication rates and major donor site morbidity in group 1 were similar or better when compared with those in group 2. The lengths of the intensive care unit (4 vs 7 days; P = .009) and hospital stays (13 vs 15 days; P = .06) were shorter in group 1. Although the microvascular success rate was similar in both groups, the local wound complication rate was significantly better for group 1. The difference for the length of intensive care unit stay was statistically significant and potentially amounts to more than 6000 dollars of savings. Functional outcomes, including the ability to tolerate oral diet, tracheostomy presence, and dental rehabilitation, were similar between the groups. CONCLUSIONS: The primary site long-term morbidity, donor site morbidity, and postoperative function of osteocutaneous radial forearm free flaps are comparable to those of other commonly used osteocutaneous free flaps such as the fibula and scapula when used in single-stage oromandibular reconstruction.     

Coordination of bowing and fingering in violin playing

Playing string instruments implies motor skills including asymmetrical interlimb coordination. How special is musical skill as compared to other bimanually coordinated, non-musical skillful performances? We succeeded for the first time to measure quantitatively bimanual coordination in violinists playing repeatedly a simple tone sequence. A motion analysis system was used to record finger and bow trajectories for assessing the temporal structure of finger-press, finger-lift (left hand), and bow stroke reversals (right arm). The main results were: (1) fingering consisted of serial and parallel (anticipatory) mechanisms; (2) synchronization between finger and bow actions varied from -12 ms to 60 ms, but these 'errors' were not perceived. The results suggest that (1) bow-finger synchronization varied by about 50 ms from perfect simultaneity, but without impairing auditory perception; (2) the temporal structure depends on a number of combinatorial mechanisms of bowing and fingering. These basic mechanisms were observed in all players, including all amateurs. The successful biomechanical measures of fingering and bowing open a vast practical field of assessing motor skills. Thus, objective assessment of larger groups of string players with varying musical proficiency, or of professional string players developing movement disorders, may be helpful in music education.     

Activation of microglia by aggregated beta-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render them protective

'Protective autoimmunity' refers to a well-controlled anti-self response that helps the body resist neurodegeneration. The response is mediated by autoimmune T cells, which produce cytokines and growth factors. Using an in vitro assay of hippocampal slices, we show that the cytokines interferon-gamma and (especially) interleukin-4, characteristic of pro-inflammatory and anti-inflammatory T cells, respectively, can make microglia neuroprotective. Aggregated beta-amyloid, like bacterial cell wall-derived lipopolysaccharide, rendered the microglia cytotoxic. Cytotoxicity was correlated with a signal transduction pathway that down-regulates expression of class-II major histocompatibility proteins (MHC-II) through the MHC-II-transactivator and the invariant chain. Protection by interleukin-4 was attributed to down-regulation of tumor necrosis factor-alpha and up-regulation of insulin-like growth factor I. These findings suggest that beneficial or harmful expression of the local immune response in the damaged CNS depends on how microglia interpret the threat, and that a well-regulated T-cell-mediated response enables microglia to alleviate rather than exacerbate stressful situations in the CNS.     

The role of HLA A2 and Cw2 in the pathogenesis of human demodicosis

BACKGROUND: Demodicosis is a chronic skin disease caused by parasitic mites of the genus Demodex. It usually affects the face area causing major esthetical problems. The pathogenesis of demodicosis is not fully understood; however, it is quite apparent that immunological mechanisms mediate its development. OBJECTIVE: The goal of this study was to study the correlation between immunological and immunogenetic data obtained from patients with demodicosis in order to clarify the pathogenesis of Demodex infestation. METHODS: Twenty-five patients with demodicosis and 13 age- and sex-matched healthy subjects participated in the study. The presence of mites was determined by microscopic inspection of sebum gland secretions. The immune response was evaluated by identifying membrane markers of different immune cells using monoclonal antibodies (anti-CD3+, CD4+, CD8+, CD16+, CD20+ and CD95+) while the concentration of IgA, IgM and IgG was measured by simple radial immunodiffusion. The level of circulating immune complexes and total hemolytic complement as well as the preparatory and digestive function of neutrophils and the functional activity of leukocytes were also studied. Patients were typed for HLA A, B, Bw and Cw using the microlymphocytotoxicity method. RESULTS: The comparison between patients with and without the A2 phenotype showed that the latter have lower numbers of CD8+, lower functional activity of leukocytes, higher concentrations of IgA, larger affected skin areas and are more often affected by deep papular and papulopustular forms of demodicosis than those with the A2 phenotype, showing that this allele has a protective role in demodicosis. Patients exhibiting the Cw2 phenotypes were rather susceptible to demodicosis. They showed decreased numbers of CD3+, increased levels of phagocytic activity, higher mite density and severer skin damage as compared to patients lacking Cw2. CONCLUSIONS: The HLA A2 and Cw2 phenotypes have an important diagnostic, prognostic and pathogenetic significance and could play a role in resistance or susceptibility to demodicosis by regulating the end phase of the immune response.     

Preimplantation genetic diagnosis for polycystic kidney disease

OBJECTIVE: To use preimplantation genetic diagnosis for achieving a polycystic kidney disease (PKD)-free pregnancy for a couple in which the female partner was affected by PKD but whose PKD1 or PKD2 carrier status was not established. DESIGN: Case report. SETTING: The IVF program of Reproductive Genetics Institute, Chicago, Illinois. PATIENT(S): An at-risk couple with the female partner affected by PKD, whose PKD1 or PKD2 carrier status was not established. INTERVENTION(S): Removal of PB1 and PB2 and testing for three closely linked markers to PKD1 (Kg8, D16S664, and SM7) and four closely linked markers to PKD2 (D4S2922, D4S2458, D4S423, and D4S1557) after standard IVF. MAIN OUTCOME MEASURE(S): Deoxyribonucleic acid analysis of PB1 and PB2 indicating whether corresponding oocytes were PKD1 or PKD2 allele free, for the purpose of transferring only embryos resulting from mutation-free oocytes. RESULT(S): Of 11 oocytes tested by PB1 and PB2 DNA analysis, 7 were predicted to contain PKD1 or PKD2, with the remaining 4 free of both mutations. Three embryos resulting from these oocytes were transferred, yielding a twin pregnancy and the birth of two unaffected children. CONCLUSION(S): This is the first preimplantation genetic diagnosis for PKD, which resulted in the birth of healthy twins confirmed to be free of PKD1 and PKD2. Preimplantation genetic diagnosis based on linked marker analysis provides an alternative for avoiding the pregnancy and birth of children with PKD, even in at-risk couples without exact PKD1 or PKD2 carrier information.     

Sucessful pregnancy outcome following three severe placental abruptions and intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation of factor V (Leiden)

A case of successful pregnancy outcome is reported in a patient with 3 preceding severe placental abruptions with intrauterine fetal death and caesarean deliveries. In the course of the current pregnancy heterozygosity for R506Q mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and low molecular weight heparin [LMWH] therapy initiated. Maternal condition was stable until delivery and all laboratory findings were within normal range. The fetus was followed up by ultrasound biometry and Doppler blood flow studies. From 28 w.g. on NST and biophysical profile were included. An emergency caesarean section was performed in 34 w.g. because of contractions not responding to tocolysis. The newborn was in good condition with weight and length corresponding to the 10th centile for gestational age [g.a]. Histologic study of the placenta showed anemic infarctions and recent haemorrhages in the basal and the chorionic plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By that moment there was already evidence of impaired fetal growth with fetal biometry corresponding to the 10th centile for g.a. After LMWH therapy was started no further slow down of fetal growth was registered. Successful pregnancy outcome may be related not only to LMWH therapy but also to other factors like active fetal monitoring after 28 w.g. and the emergency caesarian delivery immediately after the onset of uterine contractions. Patients with past obstetric history of severe preeclampsia, placental abruption or fetal growth restriction have to be screened for hereditary or acquired thrombophilia. If a thrombophillic state is present early LMWH therapy has to be considered. It is aimed to prevent anaemic placental infarctions and thrombotic complications.     

Respiratory and hemodynamic monitoring during laparoscopy and two computer-controlled TCI anesthesiologic technique

Forty women under general anaesthesia (computer-controlled TCI-infusion) in two groups were subjected to non-invasive haemodynamic monitoring together with arterial gasometry and capnography. Simultaneous continuous monitoring of aortic blood flow and PetCO2 allows an undelayed recognition of major circulatory disturbances, before significant changes in heart rate and arterial pressure occur.     

Gene transfer approaches in cancer immunotherapy

The idea of enhancing or establishing effective immune response against endogenously developed tumor cells is not novel. More than a hundred years ago, bacterial components were used to develop antitumor immune response. Later, when a number of immune system-effecting cytokines had been discovered, they were used for systemic treatment of cancer patients. However, systemic treatment often resulted in even negative outcome. Recent developments of genetic approaches of cell modifications allowed developing of modern techniques of targeted tumor cell elimination. In the present paper, we review modern trends of the antitumor response enhancement based on immunoregulatory gene transfer into different cell types both in vivo and in vitro. Almost all these approaches are based on the activation of the adaptive arm of the immune system in response to tumor cells. However, recent studies indicate that the innate arm of the immune system, as well as adaptive arm, is involved in tumor suppression. The innate immune system uses nonrearranging germline receptors, which could trigger cellular effector responses that are conditional (or instructive) to the subsequent adaptive immune response. Last years' viewpoints on 'self' and 'non-self' recognition and primary induction of the immune response have changed. The key role of lymphocytes is pathogen recognition and, following immune response induction, switched on the central role of dendritic cells in 'non-self' recognition and induction of both innate and adaptive responses. Moreover, innate response is supposed to be an essential starting point in induction of successful and effective acquired response. Most cancer vaccines do not have 'non-self' marks presentation due to their endogenous origin, thus lacking their effectiveness in the induction of the specific long-lasting immune response. Taking this point into consideration, we can conclude that to make cancer vaccine more effective we have to present tumor antigens, together with the molecules that can potentially activate downstream 'non-self' recognition events not in parallel, but as a consequence of tumor antigen processing and presentation.     

The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement

To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally or via a variable IV infusion, 80 healthy patients undergoing elective total knee replacement were studied according to a prospective, controlled, randomized, single-blinded study design. Patients were allocated to one of four treatment groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV infusion of 10 mg . kg(-1) . h(-1) was administered until 12 h after final deflation of the limb tourniquet. In group TA-short, a similar regimen was followed; however, the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet (time of discharge from the postanesthesia care unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA-oral, 60 min before surgery an oral dose of TA 1 g was administered. After surgery, a similar dose of TA was administered every 6 h for the next 18 h. In the control group, TA was not administered. At patient discharge, postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups. Because oral drug administration is simple and does not require specific infusion equipment, the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration.