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LT
Kinds of LT Terms modified by LT Selected AbstractsShort-term symptom and quality-of-life comparison between laparoscopic Nissen and Toupet fundoplicationsDISEASES OF THE ESOPHAGUS, Issue 1 2009R. Radajewski SUMMARY Laparoscopic antireflux surgery is an established method of treatment of gastroesophageal reflux disease (GERD). This study evaluates the efficacy of Nissen versus Toupet fundoplication in alleviating the symptoms of GERD and compares the two techniques for the development of post-fundoplication symptoms and quality of life (QOL) at 12 months post-surgery. In this prospective consecutive cohort study, 94 patients presenting for laparoscopic antireflux surgery underwent either laparoscopic Nissen fundoplication (LN) (n = 51) from February 2002 to February 2004 or a laparoscopic Toupet fundoplication (LT) (n = 43) from March 2004 to March 2006, performed by a single surgeon (G. S. S.). Symptom assessment, a QOL scoring instrument, and dysphagia questionnaires were applied pre- and postoperatively. At 12 months post-surgery, patient satisfaction levels in both groups were high and similar (LT: 98%, LN: 90%; P = 0.21). The proportion of patients reporting improvement in their reflux symptoms was similar in both groups (LT: 95%, LN: 92%; P = 0.68), as were post-fundoplication symptoms (LT: 30%, LN: 37%; P = 0.52). Six patients in the Nissen group required dilatation for dysphagia compared with one in the Toupet group (LT: 2%, LN: 12%; P = 0.12). One patient in the Nissen group required conversion to Toupet for persistent dysphagia (P = 0.54). In this series, overall symptom improvement, QOL, and patient satisfaction were equivalent 12 months following laparoscopic Nissen or Toupet fundoplication. There was no difference in post-fundoplication symptoms between the two groups, although there was a trend toward a higher dilatation requirement and reoperation after Nissen fundoplication. [source] Distribution, zoogeography and biology of the Murchison River hardyhead (Craterocephalus cuneiceps Whitley, 1944), an atherinid endemic to the Indian Ocean (Pilbara) Drainage Division of Western AustraliaECOLOGY OF FRESHWATER FISH, Issue 3 2005M. G. Allen Abstract , The Murchison River hardyhead (Craterocephalus cuneiceps) is endemic to the extremely arid Indian Ocean (Pilbara) Drainage Division of Western Australia, where it is found in the Greenough, Hutt, Murchison, Wooramel, Gascoyne and DeGrey rivers, but is absent from numerous rivers within its range. The most likely explanation for the disjunct contemporary distribution is that C. cuneiceps has simply never inhabited the rivers from which it is conspicuously absent (e.g. Ashburton and Fortescue). Biogeographical, geological and palaeoclimatic evidence is presented to support this hypothesis. In the Murchison River, breeding was extremely protracted with recruitment occurring throughout the year. The largest female and male specimens captured were 96 mm total length (TL; 7.73 g) and 86 mm TL (5.57 g), respectively. Sex ratio was 1.09 females:1 male. Batch fecundity ranged from 46 to 454 (mean 167.5 ± 25.7 SE). Estimates for the length at which 50 and 95% of females first spawned were 36.4 and 44.3 mm TL, respectively. Craterocephalus cuneiceps is essentially a detritivore, but also feeds on aquatic invertebrates. Rainfall in the Murchison River catchment is unpredictable and pH, salinity and temperature are variable. A specialised diet, small size and young age at maturity and protracted spawning period, coupled with serial spawning and high fecundity, allows the numerical dominance of this species in competitive, harsh, arid and unpredictable desert environments. Resumen 1. Craterocephalus cuneiceps es una especie endémica de las cuencas del Océano Indico (i.e., Pilbara) de Australia Occidental. Se encuentra en los ríos Greenough, Hutt, Murchison, Wooramel, Gascoyne y DeGrey pero está ausente en numerosos ríos dentro de su área de distribución. La explicación más probable para esta distribución separada en la actualidad es que C. cuneiceps no ha habitado nunca los ríos en los que está ausente tales como los ríos Ashburton y Fortescue. Presentamos evidencia bio-geográfica, geológica y paleo-climática para soportar esta hipótesis. 2. En el río Murchison, la reproducción es extremadamente prolongada con reclutamiento a lo largo de todo el año. Los mayores machos y hembras capturados alcanzaron 96 mm LT (7.73 g) y 86 mm LT (5.57 g), respectivamente. La proporción de sexos fue 1.09 hembras: 1 macho. La fecundidad varió entre 46 y 454 (media 167.5 ± 25.7 SE) y la longitudes a la que el 50 y el 95% de las hembras se reproducen por primera vez alcanzaron 36.4 y 44.3 mm LT, respectivamente. 3. C. cuneiceps es esencialmente detritívoro pero también se alimenta de invertebrados acuáticos. La lluvia sobre la cuenca del río Murchison es impredecible y el pH, la salinidad y la temperatura son variables. Una dieta especializada, pequeño tamaño, una edad joven en la madurez, y un período reproductivo prolongado, ademos de una freza seriada y alta fecundidad, permiten la dominancia numérica de la especie en ambientes competitivos, duros, áridos e impredecibles. [source] Voltammetry as a Virtual Potentiometric Sensor in Modeling of a Metal-Ligand System and Refinement of Stability Constants.ELECTROANALYSIS, Issue 8 2004Part 1. Abstract A mathematical conversion of data coming from nonequilibrium and dynamic voltammetric techniques (a direct current sampled (DC) and differential pulse (DP) polarography) into potentiometric sensor type of data is described and tested on a dynamic metal-ligand system. A combined experiment involving DCP, DPP and glass electrode potentiometry (GEP) was performed on a single solution sample containing a fixed [LT],:,[MT] ratio (acid-base titration). Dedicated potentiometric software ESTA was successfully employed in the refinement operations performed on virtual potentiometric (VP) data obtained from DC and DP polarography. It was possible to refine stability constants either separately, from VP-DC or VP-DP, or simultaneously from any combination of VP-DC, VP-DP and GEP. The concept of VP-DC or VP-DP is reported for the first time and numerous documented and possible advantages are discussed. The proposed procedure can be easily utilized also by nonelectrochemists who are interested in, e.g., the ligand design strategies. [source] Long-term clopidogrel administration following severe coronary injury reduces proliferation and inflammation via inhibition of nuclear factor-kappaB and activator protein 1 activation in pigsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2009K. Pels ABSTRACT Background, The optimal duration of clopidogrel treatment following percutaneous coronary intervention (PCI) and the patient population that would benefit most are still unknown. In a porcine coronary injury model, we tested two different durations of clopidogrel treatment on severely or moderately injured arteries and examined the arterial response to injury. To understand the molecular mechanism, we also investigated the effects on transcription factors nuclear factor-kappaB (NF-,B) and activator protein 1 (AP-1). Materials and methods, In 24 cross-bred pigs, one coronary artery was only moderately injured by percutaneous transluminal coronary angioplasty (PTCA) and one coronary artery was severely injured by PTCA and subsequent beta-irradiation (Brachy group). Animals received 325 mg aspirin daily for 3 months and 75 mg clopidogrel daily for either 28 days [short-term (ST) clopidogrel group] or 3 months [long-term (LT) clopidogrel group]. Results, After 3 months, the number of proliferating cells per cross-section differed significantly between ST and LT in both injury groups (PTCAST 90·2 ± 10·3 vs. PTCALT 19·2 ± 4·7, P < 0·05; BrachyST 35·8 ± 8·4 vs. BrachyLT 7·5 ± 2·0, P < 0·05). Similar results were seen for inflammatory cells (CD3+ cells): PTCAST 23·5 ± 3·55 vs. PTCALT 4·67 ± 0·92, P < 0·05; BrachyST 83·17 ± 11·17 vs. BrachyLT 20 ± 4·82, P < 0·05). Long-term administration also reduced the activity of NF-,B and AP-1 by 62,64% and 42,58%, respectively. However, the effects of different durations of clopidogrel administration on artery dimensions were not statistically significant. Conclusions, Regarding inflammation and transcription factor activity at the PCI site, long-term clopidogrel administration is superior to short-term administration, especially in severely injured arteries. Transferring our results to the human situation, patients with more severely diseased arteries may benefit from a prolonged clopidogrel medication after PCI. [source] The expression of cytosolic phospholipase A2 and biosynthesis of leukotriene B4 in acute myeloid leukemia cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007Gudmundur Runarsson Abstract Leukotrienes (LT) exert stimulatory effects on myelopoiesis, beside their inflammatory and immunomodulating effects. Here, we have studied the expression and activity of the enzymes involved in the synthesis of leukotriene B4 (LTB4) in acute myeloid leukemia (AML) cells (16 clones) and G-CSF mobilized peripheral blood CD34+ cells. CD34+ cells from patients with non-myeloid malignancies expressed cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase activating protein (FLAP), and leukotriene A4 (LTA4) hydrolase but not 5-lipoxygenase (5-LO). The enzyme cPLA2 was abundantly expressed in AML cells and the activity of the enzyme was high in certain AML clones. The expression of 5-LO, FLAP, and LTA4 hydrolase in AML clones was in general lower than in healthy donor polymorphonuclear leukocytes (PMNL). The calcium ionophore A23187-induced release of [14C] arachidonic acid (AA) in AML cells was low, compared with PMNL, and did not correlate with the expression of cPLA2 protein. Biosynthesis of LTB4, upon calcium ionophore A23187 activation, was only observed in five of the investigated AML clones and only three of the most differentiated clones produced similar amounts of LTB4 as PMNL. The capacity of various cell clones to produce LTs could neither be explained by the difference in [1 , 14C] AA release nor 5-LO expression. Taken together, these results indicate that LT synthesis is under development during early myelopoiesis and the capacity to produce LTs is gained upon maturation. High expression of cPLA2 in AML suggests a putative role of this enzyme in the pathophysiology of this disease. [source] Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006Carrie Abstract B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival factor required for B cell maturation. BAFF transgenic (Tg) mice develop autoimmune disorders characterized by autoantibody production, which leads to nephritis and salivary gland destruction (sialadenitis), features reminiscent of systemic lupus erythematosus and Sjögren's syndrome (SS), respectively. Disease in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell compartment and the abnormal presence of MZ-like B cells in the blood, LN and inflamed salivary glands, suggesting a role for these cells in BAFF-induced autoimmunity. Lymphotoxin-, (LT,)-deficient mice show disrupted splenic architecture, lack MZ B cells and some peripheral LN, and are unable to mount T cell-dependent immune responses. BAFF Tg mice lacking LT, (LT,,-BTg) retained these defects, yet still developed nephritis associated with the presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice, aging LT,,-BTg mice no longer developed sialadenitis. Thus, autoimmune disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells at separate anatomical sites. [source] Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2006Stephan Göttig Abstract To investigate the role of the monomeric guanosine triphosphatase (GTPase) Rho on migration of hematopoietic progenitor cells (HPC), we employed different clostridial toxins which inhibit the Rho family of GTPases. Pretreatment with C2I-C3, a cell-accessible C3 transferase fusion protein that targets Rho, increased chemokinetic migration of the factor-dependent multipotent cell line Factor Dependent Cell Paterson with mixed lineage differentiation potential (FDCP-mix) and of primary lineage marker-depleted HPC in vitro. In contrast, treatment with lethal toxin (LT) from Clostridium sordellii, which predominantly inactivates Rac, and with toxin,B from C.,difficile, which inactivates Rho, Rac and Cdc42, decreased in vitro migration. When HPC pretreated with LT or toxin,B were transplanted into mice, homing to the bone marrow was impaired, whereas C2I-C3 treatment did not alter HPC homing. However, in a competitive hematopoietic repopulation experiment in C57BL/6 mice, pretreatment of bone marrow cells with any of the inhibitors, including the Rho inhibitor C2I-C3, resulted in suppressed donor-type hematopoiesis. Our data indicate that whereas Rac supports HPC cell cycling, migration, short-term homing and hematopoietic regeneration, Rho coordinates down-regulation of HPC migration and is required for hematopoietic regeneration. [source] Lymphotoxin,, receptor-Ig fusion protein treatment blocks actively induced, but not adoptively transferred, uveitis in Lewis ratsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Hui Shao Abstract Previous studies have shown that treatment of rodents with a lymphotoxin (LT),, receptor-Ig fusion protein (LT,R-Ig), which binds to both LT and LIGHT, prevents the development of autoimmune diseases, but the mechanism involved is unclear. To explore the potential role of LT or LIGHT in the pathogenesis of autoimmune uveitis, uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid-binding protein, or by adoptive transfer of R16-specific T,cells. Interestingly, LT,R-Ig treatment completely prevented actively induced uveitis, but not the adoptively transferred disease. We also show that LT,R-Ig-treated R16-injected rats had a significantly decreased T,cell response to R16 and that herpesvirus entry mediator (HVEM)-Ig, a fusion protein that blocks LIGHT, also inhibited disease development. Our results suggest that LT or LIGHT plays a critical role in the induction, rather than the effector, phase of the disease. [source] First Hexanuclear UIV and ThIV Formate Complexes , Structure and Stability Range in Aqueous SolutionEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 32 2009Shinobu Takao Abstract The actinide(IV) hexanuclear [M6(,3 -O)4(,3 -OH)4(HCOO)12(LT)6] complexes were prepared (LT = H2O or CH3OH). Their structures were investigated by single-crystal X-ray analysis and XAFS spectroscopy. HCOO, acts as a bridging ligand, which prevents the formation of polynuclear hydrolysis species like UIV hydrous oxide colloids at least up to pH = 3.25, and stabilizes the nanosized clusters in solution. The charge of the hexamer is balanced by the O/OH ratio of the ,3 -bridges.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Valence-Tautomeric RbMnFe Prussian Blue Analogues: Composition and Time Stability InvestigationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 6 2009Lionel Salmon Abstract Three different stoichiometric forms of RbxMn[Fe(CN)6]y·zH2O [x = 0.96, y = 0.98, z = 0.75 (1); x = 0.94, y = 0.88, z = 2.17 (2); x = 0.61, y = 0.86, z = 2.71 (3)] Prussian blue analogues were synthesized and investigated by magnetic, calorimetric, Raman spectroscopic, X-ray diffraction, and 57Fe Mössbauer spectroscopic methods. Compounds 1 and 2 show a hysteresis loop between the high-temperature (HT) FeIII(S = 1/2),CN,MnII(S = 5/2) and the low-temperature (LT) FeII(S = 0),CN,MnIII(S = 2) forms of 61 and 135 K width centered at 273 and 215 K, respectively, whereas the third compound remains in the HT phase down to 5 K. The splitting of the quadrupolar doublets in the 57Fe Mössbauer spectra reveal the electron-transfer-active centers. Refinement of the X-ray powder diffraction profiles shows that electron-transfer-active materials have the majority of the Rb ions on only one of the two possible interstitial sites, whereas nonelectron-transfer-active materials have the Rb ions equally distributed. Moreover, the stability of the compounds with time and following heat treatment is also discussed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] The application of modified lapped transform domain median filter to narrow,band interference excision in DSSS systemsEUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 4 2001Chongni Li Guangruihu A novel communication receiver which uses lapped transform (LT) incorporating modified median filter (MMF) algorithm is designed for narrow,band interference (NB1) excision. Comparing to traditional Fourier Transform, LT has longer basis vectors, less spectral leakage, thus better frequency resolution. The LT domain MMF algorithm takes full advantages of the direct sequence spread spectrum signal, as well as the characteristics of LT, performs the transform domain filtering twice. The first filtering locates the position of interference and mitigates most of them. The second filtering was performed in a small neighborhood of the located interference. So LT domain MMF algorithm can completely mitigate the interference without distorting the desired signal. Simulation results demonstrated the improved BER performance and increased robustness of our approach. [source] Effects of Ischaemia on Subsequent Exercise-Induced Oxygen Uptake Kinetics in Healthy Adult HumansEXPERIMENTAL PHYSIOLOGY, Issue 2 2002Michael L. Walsh Leg muscles were occluded (33 kPa) prior to exercise to determine whether the induced metabolic changes, and reactive hyperaemia upon occlusion release just prior to the exercise, would accelerate the subsequent oxygen consumption (V,O2) response. Eight subjects performed double bouts (6 min duration, 6 min rest in-between) of square wave leg cycle ergometry both below and above their lactate threshold (LT). Prior to exercise, large blood pressure cuffs were put around the upper thighs. Occlusion durations were 0 min (control), 5 min and 10 min. Ischaemia was terminated within 5 s prior to exercise onset. Heart rate, V,O2, ventilatory rate (V,E), electromyogram (EMG) and haemoglobin/myoglobin (Hb/Mb) saturation were recorded continuously. Single exponential modelling demonstrated that, compared to control (time constant = 53.9 ± 13.9 s), ischaemia quickened the V,O2 response (P < 0.05) for the first bout of exercise above LT (time constant = 48.3 ± 14.5 s) but not to any other exercise bout below or above LT. The 3-6 min integrated EMG (iEMG) slope was correlated to the 3-6 min V,O2 slope (r = 0.73). Hb/Mb saturation verified the ischaemia but did not show a consistent relation to the V,O2 time course. Reactive hyperaemia induced a faster V,O2 response for work rates above LT. The effect, while significant, was not large considering the expected favourable metabolic and circulatory changes induced by ischaemia. [source] EMG and Oxygen Uptake Responses During Slow and Fast Ramp Exercise in HumansEXPERIMENTAL PHYSIOLOGY, Issue 1 2002Barry W. Scheuermann This study examined the relationship between muscle recruitment patterns using surface electromyography (EMG) and the excess O2 uptake (ExV,O2) that accompanies slow (SR, 8 W min,1) but not fast (FR, 64 W min,1) ramp increases in work rate (WR) during exercise on a cycle ergometer. Nine subjects (2 females) participated in this study (25 ± 2 years, ± S.E.M.). EMG was obtained from the vastus lateralis and medialis and analysed in the time (root mean square, RMS) and frequency (median power frequency, MDPF) domain. Results for each muscle were averaged to provide an overall response and expressed relative to a maximal voluntary contraction (%MVC). ,V,O2/,WR was calculated for exercise below (S1) and above (S2) the lactate threshold (LT) using linear regression. The increase in RMS relative to the increase in WR for exercise below the LT (,RMS/,WR-S1) was determined using linear regression. Due to non-linearities in RMS above the LT, ,RMS/,WR-S2 is reported as the difference in RMS (,RMS) and the difference in WR (,WR) at end-exercise and the LT. SR was associated with a higher (P < 0.05) ,V,O2/,WR (S1, 9.3 ± 0.3 ml min,1 W,1; S2, 12.5 ± 0.6 ml min,1 W,1) than FR (S1, 8.5 ± 0.4 ml min,1 W,1; S2, 7.9 ± 0.4 ml min,1 W,1) but a similar ,RMS/,WR-S1 (SR, 0.11 ± 0.01% W,1; FR, 0.10 ± 0.01% W,1). ExV,O2 was greater (P < 0.05) in SR (3.6 ± 0.7 l) than FR (-0.7 ± 0.4 l) but was not associated with a difference in either ,RMS/,WR-S2 (SR, 0.14 ± 0.01% W,1; FR, 15 ± 0.02% W,1) or MDPF (SR, 2.6 ± 5.9%; FR, -15.4 ± 4.5%). The close matching between power output and RMS during SR and FR suggests that the ExV,O2 of heavy exercise is not associated with the recruitment of additional motor units since ExV,O2 was observed during SR only. Compared to the progressive decrease in MDPF observed during FR, the MDPF remained relatively constant during SR suggesting that either (i) there was no appreciable recruitment of the less efficient type II muscle fibres, at least in addition to those recruited initially at the onset of exercise, or (ii) the decrease in MDPF associated with fatigue was offset by the addition of a higher frequency of type II fibres recruited to replace the fatigued motor units. [source] Vulnerability of African mammals to anthropogenic climate change under conservative land transformation assumptionsGLOBAL CHANGE BIOLOGY, Issue 3 2006WILFRIED THUILLER Abstract Recent observations show that human-induced climate change (CC) and land transformation (LT) are threatening wildlife globally. Thus, there is a need to assess the sensitivity of wildlife on large spatial scales and evaluate whether national parks (NPs), a key conservation tools used to protect species, will meet their mandate under future CC and LT conditions. Here, we assess the sensitivity of 277 mammals at African scale to CC at 10, resolution, using static LT assumptions in a ,first-cut' estimate, in the absence of credible future LT trends. We examine the relationship between species' current distribution and macroclimatic variables using generalized additive models, and include LT indirectly as a filter. Future projections are derived using two CC scenarios (for 2050 and 2080) to estimate the spatial patterns of loss and gain in species richness that might ultimately result. We then apply the IUCN Red List criteria A3(c) of potential range loss to evaluate species sensitivity. We finally estimate the sensitivity of 141 NPs in terms of both species richness and turnover. Assuming no spread of species, 10,15% of the species are projected to fall within the critically endangered or extinct categories by 2050 and between 25% and 40% by 2080. Assuming unlimited species spread, less extreme results show proportions dropping to approximately 10,20% by 2080. Spatial patterns of richness loss and gain show contrasting latitudinal patterns with a westward range shift of species around the species-rich equatorial zone in central Africa, and an eastward shift in southern Africa, mainly because of latitudinal aridity gradients across these ecological transition zones. Xeric shrubland NPs may face significant richness losses not compensated by species influxes. Other NPs might expect substantial losses and influxes of species. On balance, the NPs might ultimately realize a substantial shift in the mammalian species composition of a magnitude unprecedented in recent geological time. To conclude, the effects of global CC and LT on wildlife communities may be most noticeable not as a loss of species from their current ranges, but instead as a fundamental change in community composition. [source] Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation,HEPATOLOGY, Issue 1 2010José A. Carrión Significant liver fibrosis (F , 2) and portal hypertension (hepatic venous pressure gradient [HVPG] , 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa × month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. Figures were almost identical for patients with HVPG , 6 mmHg or HVPG < 6 mmHg at 1 year after LT. Multivariate analysis identified donor age, bilirubin level, and LSM as independent predictors of fibrosis progression and portal hypertension in the estimation group (n = 50) and were validated in a second group of 34 patients. The areas under the receiver operating characteristic curve that could identify rapid fibrosers and patients with portal hypertension as early as 6 months after LT were 0.83 and 0.87, respectively, in the estimation group and 0.75 and 0.80, respectively, in the validation group. Conclusion: Early and repeated LSM following hepatitis C recurrence in combination with clinical variables discriminates between rapid and slow fibrosers after LT. (HEPATOLOGY 2009.) [source] Smoking and hypoxemia caused by hepatopulmonary syndrome before and after liver transplantationHEPATOLOGY, Issue 2 2001Giovanni Rolla Severe hypoxemia may occur in patients with liver disease as a result of abnormal intrapulmonary vasodilatations (hepatopulmonary syndrome, HPS). Liver transplantation (LT) is the only effective treatment of HPS, with a quite variable delay of improvement of oxygenation. Smoking, by decreasing respiratory nitric oxide (NO), apparently contributed to improved oxygenation in a 44-year-old man with alcohol-induced cirrhosis, complicated by HPS, who underwent LT. The patient quit smoking just before LT, when his PaO2 was 29 mm Hg and exhaled NO (eNO) 28 ppb, a value far above the normal limits (9.6 ± 3.2 ppb). After LT, oxygenation remained poor and eNO remained high for more than 4 months, when the patient started to smoke again (blood HbCO going up to 5%). At that time eNO decreased to 6 ppb and PaO2 increased to 67 mm Hg. The strict relationship between eNO and oxygenation observed in this case reinforces the hypothesis that NO is the most important vasodilating mediator in HPS. Smoking may have hastened the resolution of HPS after LT by inhibiting respiratory NO and/or through a generalized impairment of endothelium-dependent vasodilation. [source] Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantationHEPATOLOGY, Issue 5 2000Raghavakaimal Sreekumar Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre- and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (,109 copies/mL, n = 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r = .56, P , .001) and 3 years (r = .53, P = .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. Higher pre- and early post-LT HCV-RNA levels are associated with more severe recurrence of HCV. The correlation of early HAI with subsequent FS suggests that higher mean HAI will eventually translate into more advanced stages of fibrosis. Patients at risk for more severe post-LT recurrence of HCV can be identified by early posttransplant HCV-RNA levels. [source] Double-dose double-phase use of second generation hepatitis B virus vaccine in patients after living donor liver transplantation: Not an effective measure in transplant recipientsHEPATOLOGY RESEARCH, Issue 1 2009Noriyo Yamashiki Aims:, Post-transplant active immunization for chronic hepatitis B patients has been attempted in several studies with controversial results. We assessed the effect of a double-dose double-phase vaccination regimen among partial living donor liver recipients. Methods:, Eighteen patients who underwent liver transplantation (LT) for chronic hepatitis B and two non-hepatitis B virus (HBV)-infected patients who received hepatitis B core antibody (HBcAb)-positive donor organs were recruited 18,78 months after LT. All were on hepatitis B immunoglobulin (HBIG) mono-prophylaxis before and throughout vaccination, to maintain hepatitis B surface antibody (HBsAb) titers of more than 100 IU/mL. Recombinant hepatitis B surface antigen vaccine (40 µg) was administered intramuscularly during weeks 0, 4, 8, 24, 28 and 32. Results:, The patients consisted of 15 males and five females with a median age of 52 (39,59) years. None developed a sufficient HBsAb titer above 500 IU/mL by week 48. In two patients whose maximum HBsAb titer increased to above 300 IU/mL, we attempted to skip HBIG, but shortly thereafter the titer dropped below 100 IU/mL and HBIG administration was resumed. Although the HBIG dose was reduced during and after vaccination, cessation of administration was not achieved. Conclusion:, Double-dose double-phase use of second generation recombinant vaccine was not effective in this study population. The selected population should be targeted for a conventional vaccine regimen, and different approaches, such as strong adjuvant or pre-S containing protein, should be further tested in a larger number of patients after LT for chronic hepatitis B. [source] Recurrence of primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation in JapanHEPATOLOGY RESEARCH, Issue 2007Satoshi Yamagiwa Although there was some initial controversy, there is now a consensus that primary biliary cirrhosis (PBC) does indeed recur in both cadaveric and living donated allografts. Recurrence rate after deceased donor liver transplantation (LT) was reported to be 10.9,23% at 5 years. In the present study, we reviewed 221 PBC patients who underwent living-donor liver transplantation (LDLT) in Japan. The 5-year overall survival rate was 79%, and the rate of recurrence based on histological findings was 10% (7/70) after a median time of 36 months. Primary immunosuppression, withdrawal of corticosteroids and human leukocyte antigen matches were not associated with the recurrence. Recurrent PBC appears to have little impact on graft function and survival, but this may become a greater problem with longer follow up. It is noteworthy that the 10-year survival of primary sclerosing cholangitis (PSC) patients who underwent LDLT wasfound to be only 39.1% in Japan, whereas that of PBC was 72.9%. Factors associated with the poor prognosis include biliary strictures, hepatobiliary and colorectal malignancies, and recurrence of PSC. In our study, we reviewed 66 patients with PSC who underwent LDLT in Japan. The 5-year survival rate was 72%, and the rate of recurrence diagnosed on histological and cholangiographic findings was 25% (11/44). Well-defined diagnostic criteria and longer studies are required to characterize the nature of recurrent PSC and its impact on graft survival in more detail. [source] Rescue policy for discarded liver grafts: a single-centre experience of transplanting livers ,that nobody wants'HPB, Issue 8 2010Lucas McCormack Abstract Background:, There is a worldwide need to expand the donor liver pool. We report a consecutive series of elective candidates for liver transplantation (LT) who received ,livers that nobody wants' (LNWs) in Argentina. Methods:, Between 2006 and 2009, outcomes for patients who received LNWs were analysed and compared with outcomes for a control group. To be defined as an LNW, an organ is required to fulfil two criteria. Firstly, each liver must be officially offered and refused more than 30 times; secondly, the liver must be refused by at least 50% of the LT programmes in our country before our programme can accept it. Principal endpoints were primary graft non-function (PNF), mortality, and graft and patient survival. Results:, We transplanted 26 LNWs that had been discarded by a median of 12 centres. A total of 2666 reasons for refusal had been registered. These included poor donor status (n= 1980), followed by LT centre (n= 398) or recipient (n= 288) conditions. Incidences of PNF (3.8% vs. 4.0%), in-hospital mortality (3.8% vs. 8.0%), 1-year patient (84% vs. 84%) and graft (84% vs. 80%) survival were equal in the LNW and control groups. Conclusions:, Transplantable livers are unnecessarily discarded by the transplant community. External and internal supervision of the activity of each LT programme is urgently needed to guarantee high standards of excellence. [source] Liver transplantation for the sequelae of intra-operative bile duct injuryHPB, Issue 3 2002E De Santibañes Background Intra-operative bile duct injuries (IBDI) are potentially severe complications of the treatment of benign conditions, with unpredictable long-term results. Multiple procedures are frequently needed to correct these complications. In spite of the application of these procedures, patients with severe injuries can develop irreversible liver disease. Liver transplantation (LT) is currently the only treatment available for such patients, but little information has been published concerning the results of LT. Methods Eight patients with LT for end-stage liver disease for IBDI were studied retrospectively. They had failure of multiple previous treatments and experienced recurrent episodes of cholangitis, oesophageal variceal bleeding, severe pruritus, refractory ascites and spontaneous peritonitis. Results Mean recipient hepatectomy time was of 243 minutes (range 140,295 min), the complete procedure averages 545 minutes (260,720) and intraoperative red-blood-cells consumption was 6.5 units (1,7). One patient required reoperation due to perforation of a Roux-en-Y loop, and three developed minor complications (2 wound infections, 1 inguinal lymphocele). One patient died due to nosocomial pneumonia (mortality rate 12.5%). One patient required retransplantation due to delayed hepatic artery thrombosis. At follow-up 75% of patients are alive with normal graft function and an excellent quality of life. Conclusions LT represents a safe curative treatment for end-stage liver disease after IBDI, albeit a major undertaking in the context of a surgical complication in the treatment of benign disease. The complications of the surgical procedure and the long-standing immunosupression impart a high cost for resolutions of these sequelae but LT represents the only long-term effective treatment for these selected patients. [source] Inhibition of the lymphotoxin pathway as a therapy for autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2008Jeffrey L. Browning Summary: The lymphotoxin (LT) system is part of the tumor necrosis factor family and is required for lymph node development. It has provided a wonderful tool for the dissection of processes critical not only for lymphoid organ development but also the maintenance of the adult immune architecture and the formation of ectopic organized lymphoid tissues in chronically inflamed sites. A soluble lymphotoxin-, receptor-immunoglobulin (LT,R-Ig) fusion protein can block this pathway and is currently being tested in the treatment of autoimmune disease. This review focuses on the immunological consequences of combined LT and LIGHT inhibition with LT,R-Ig administration as distinct from the developmental biology. [source] Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulationIMMUNOLOGICAL REVIEWS, Issue 1 2007Joshua A. Boyce Summary:, When activated by specific antigen, complement, or other transmembrane stimuli, mast cells (MCs) generate three eicosanoids: prostaglandin (PG)D2, leukotriene (LT)B4, and LTC4, the parent molecule of the cysteinyl leukotrienes (cysLTs). These diverse lipid mediators, which are generated from a single cell membrane-associated precursor, arachidonic acid, can initiate, amplify, or dampen inflammatory responses and influence the magnitude, duration, and nature of subsequent immune responses. PGD2 and cysLTs, which were originally recognized for their bronchoconstricting and vasoactive properties, also serve diverse and pivotal functions in effector cell trafficking, antigen presentation, leukocyte activation, matrix deposition, and fibrosis. LTB4 is a powerful chemoattractant for neutrophils and certain lymphocyte subsets. Thus, MCs can contribute to each of these processes through eicosanoid generation. Additionally, MCs express G-protein-coupled receptors specific for cysLTs, LTB4, and another eicosanoid, PGE2. Each of these receptors can regulate MC functions in vivo by autocrine and paracrine mechanisms. This review focuses on the biologic functions for MC-associated eicosanoids, the regulation of their production, and the mechanisms by which eicosanoids may regulate MC function in host defense and disease. [source] Lymphotoxin and LIGHT signaling pathways and target genesIMMUNOLOGICAL REVIEWS, Issue 1 2004Kirsten Schneider Summary:, Lymphotoxins (LT, and LT,), LIGHT [homologous to LT, inducible expression, competes with herpes simplex virus (HSV) glycoprotein D for HSV entry mediator (HVEM), a receptor expressed on T lymphocytes], tumor necrosis factor (TNF), and their specific receptors LT,R, HVEM, and TNF receptor 1 (TNFR1) and TNFR2, form the immediate family of the larger TNF superfamily. These cytokines establish a critical communication system required for the development of secondary lymphoid tissues; however, knowledge of the target genes activated by these signaling pathways is limited. Target genes regulated by the LT,,-LT,R pathway include the tissue-organizing chemokines, CXCL13, CCL19, and CCL21, which establish cytokine circuits that regulate LT expression on lymphocytes, leading to organized lymphoid tissue. Infectious disease models have revealed that LT,, pathways are also important for innate and adaptive immune responses involved in host defense. Here, regulation of interferon-, by LT,R and TNFR signaling may play a crucial role in certain viral infections. Regulation of autoimmune regulator in the thymus via LT,R implicates LT/LIGHT involvement in central tolerance. Dysregulated expression of LIGHT overrides peripheral tolerance leading to T-cell-driven autoimmune disease. Blockade of TNF/LT/LIGHT pathways as an intervention in controlling autoimmune diseases is attractive, but such therapy may have risks. Thus, identifying and understanding the target genes may offer an opportunity to fine-tune inhibitory interventions. [source] Lymphoid microenvironment in the gut for immunoglobulin A and inflammationIMMUNOLOGICAL REVIEWS, Issue 1 2003Robert Chin Summary:, Signaling through lymphotoxin , receptor (LT,R) initiates the unfolding of a host of developmental programs ranging from the organogenesis of lymph nodes and Peyer's patches (PPs) to the coordination of splenic microarchitecture. While investigating an alternative pathway to immunoglobulin A (IgA) production, it was uncovered that LT,R signaling in the lamina propria (LP) stroma orchestrates the coordinated expression of key chemokines and adhesion molecules, creation of a cytokine milieu, and stroma development that facilitates robust IgA production independent of secondary lymphoid structures. Simultaneously, this same infrastructure can be commandeered by autoreactive T cells to organize both the acute destruction of the intestinal mucosa and chronic intestinal inflammation via the ligands for LT,R. The ability to modulate LT,R signaling may alternatively permit the suppression of autoimmune responses and augmentation of gut defenses. [source] Characterization of the migration of lung and blood T cells in response CXCL12 in a three-dimensional matrixIMMUNOLOGY, Issue 4 2010Caroline E. Day Summary The ability of T cells to microlocalize within tissues, such as the lung, is crucial for immune surveillance and increased T-cell infiltration is a feature of many inflammatory lung conditions. T-cell migration has mainly been studied in two-dimensional assays. Using three-dimensional collagen gels to mimic the extracellular matrix of lung tissue, we have characterized the migration of T lymphocytes isolated from peripheral blood (PBT) and lung (LT) in response to interleukin-2 (IL-2) and CXCL12. Freshly isolated PBT and LT showed a low degree of migration (blood 4·0 ± 1·3% and lung 4·1 ± 1·7%). Twenty-four hours of culture increased the percentage of migrating PBT and LT (blood 17·5 ± 2·9% and lung 17·7 ± 3·8%). The IL-2 stimulation modestly increased migration of PBT after 6 days (32·3 ± 6·0%), but had no effect on the migration of LT (25·5 ± 3·2%). Twenty-four hours of stimulation with anti-CD3/CD28 caused a small but significant increase in the migration of PBT (to 36·4 ± 5·8%). In a directional three-dimensional assay, CXCL12 failed to induce migration of fresh PBT or LT. Twenty-four hours of culture, which increased CXCR4 expression of PBT 3·6-fold, significantly increased the migration of PBT in response to CXCL12. Migration of PBT to CXCL12 was blocked by pertussis toxin, but not by the phosphoinositide 3-kinase inhibitor wortmannin. Twenty-four-hour cultured LT did not respond to CXCL12. CD3/CD28-stimulation inhibited CXCL12-mediated migration of PBT. These results suggest that the migration pattern of PBT is distinct from that of LT. [source] Anti-inflammatory effects in the skin of thymosin-,4 splice-variantsIMMUNOLOGY, Issue 1 2003Michael Girardi Summary The intraepithelial lymphocyte (IEL) network of T-cell receptor ,,+ (V,5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-,4 (T,4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UT,4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LT,4) with unknown bioactivity. Freshly isolated V,5+ DETCs expressed both forms, while only LT,4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LT,4 and UT,4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad ,-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LT,4 were broader and most often stronger than those of UT,4. Thus, the activation-responsive expression of the lymph-specific form of T,4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation. [source] Transcutaneous delivery and thermostability of a dry trivalent inactivated influenza vaccine patchINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 2 2008Vladimir G. Frolov A patch containing a trivalent inactivated influenza vaccine (TIV) was prepared in a dried, stabilized formulation for transcutaneous delivery. When used in a guinea pig immunogenicity model, the dry patch was as effective as a wet TIV patch in inducing serum anti-influenza IgG antibodies. When the dry TIV patch was administered with LT as an adjuvant, a robust immune response was obtained that was comparable with or better than an injected TIV vaccine. When stored sealed in a nitrogen-purged foil, the dry TIV patch was stable for 12 months, as measured by HA content, under both refrigerated and room temperature conditions. Moreover, the immunological potency of the vaccine product was not affected by long-term storage. The dry TIV patch was also thermostable against three cycles of alternating low-to-high temperatures of ,20/25 and ,20/40°C, and under short-term temperature stress conditions. These studies indicate that the dry TIV patch product can tolerate unexpected environmental stresses that may be encountered during shipping and distribution. Because of its effectiveness in vaccine delivery and its superior thermostable characteristics, the dry TIV patch represents a major advance for needle-free influenza vaccination. [source] Extubation score in the operating room after liver transplantationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010S. SKURZAK Background: Early extubation after liver transplantation (LT) is an increasingly applied safe practice. The aim of the present study was to provide a simple extubation rule for accelerated weaning in the operating room (OR). Methods: Data of 597 patients transplanted at the LT center of Turin (Italy) were retrospectively analyzed. Fifty-two nonextubated patients (excluding those with a scheduled early reoperation) were compared with 545 successfully extubated patients (not in need of reintubation within the first 48 h). Significant variables at univariate analysis were entered into a logistic regression model and the regression coefficients of independent predictors were used to yield a prognostic score called the safe operating room extubation after liver transplantation (SORELT) score. Results: Two major and three minor criteria were found. The major ones were blood transfusions (higher than/or equal to 7 U of packed red blood cells) and end of surgery lactate (higher than/or equal to 3.4 mmol/l). The minor ones were status before LT (home vs. hospitalized patient), duration of surgery (longer than/or equal to 5 h), vasoactive drugs at the end of surgery (dopamine higher than 5 ,g/kg/min or norepinephrine higher than 0.05 ,g/kg/min). Patients who fulfill the SORELT score-derived criteria (fewer than two major/one major plus two minor/three minor criteria) can be considered for OR extubation. Conclusion: Early extubation after LT requires a very careful assessment of the pre-operative, intraoperative, graft and post-operative care data available. The SORELT score helps as a simple and objective aid in considering such a decision. [source] Oral acanthosis nigricans, tripe palms and sign of leser-trélat in a patient with gastric adenocarcinomaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2004M. Pentenero DDS Acanthosis nigricans (AN), tripe palms (TP) and the sign of Leser-Trélat (LT) may be seen with the presence of malignancy. Acanthosis nigricans may have a mucocutaneous localization involving the oral mucosa with papillomatous and verrucous lesions usually on the lips and buccal mucosa. These paraneoplastic dermatoses are generally linked with intra-abdominal malignancy, most often gastric adenocarcinoma. Improvement of the associated dermatoses after the treatment of the malignancy has been frequently observed. We report the case of a 53-year-old man suffering from advanced gastric adenocarcinoma, in which metastases seemed to sustain all three paraneoplastic dermatoses. To the best of our knowledge this is the first case of a patient showing manifestations of all three paraneoplastic dermatoses. Patients presenting with this set of dermatoses should be suspected to harbor an occult malignancy, or have persistence of a known malignancy. [source] | ||||||||||||||||||||||||||||||||||||||||