El trasplante hepático aumenta la resecabilidad R0 y la supervivencia de los pacientes con tumor de Klatskin irresecable no diseminado

IntroductionThere are no established indications for Liver transplant (LT) in patients with a Klatskin tumour (KT) due to the differences in the published results.ObjectiveTo report on our patients who have non-disseminated unresectable KT and who were given a LT, and to compare results with those of patients who have had tumour resection and those who have not.Patients and methodWe have treated 75 patients diagnosed with KT. The mean age was 62±11 years (range: 38–88 years) and 50 were males (66%). Twenty patients were inoperable. Of the 55 patients who underwent surgery: tumour resection (TR) was performed in 29 cases; there was no tumour dissemination in 11 unresectable cases and therefore these patients were added to the LT waiting list and the remaining 15 unresectable cases had tumour dissemination and remained on palliative treatment.ResultsIn the LT group there was no postoperative mortality (during the first month) and the survival rate was 95%, 59% and 36% with a disease-free survival of 75%, 40% and 20%; whereas the patients given RT had a survival rate of 80%, 52% and 38% at 1, 3 and 5 years, with a disease-free survival of 65%, 35% and 19%, without any differences compared to the LT group. Patients with unresectable tumour left on palliative therapy had a lower survival than the unresectable who underwent LT (p<0.001).ConclusionsIn patients with non-disseminated unresectable KT, LT has a similar survival to that obtained in cases with resectable R0 liver resection. LT improves the survival rate achieved using palliative treatment in patients with non-disseminated unresectable KT.     

Game Related Statistics Which Discriminate Between Winning and Losing Under-16 Male Basketball Games

The aim of the present study was to identify the game-related statistics which discriminate between winning and losing teams in under-16 years old male basketball games. The sample gathered all 122 games in the 2004 and 2005 Under-16 European Championships. The game-related statistics analysed were the free-throws (both successful and unsuccessful), 2- and 3-points field-goals (both successful and unsuccessful) offensive and defensive rebounds, blocks, assists, fouls, turnovers and steals. The winning teams exhibited lower ball possessions per game and better offensive and defensive efficacy coefficients than the losing teams. Results from discriminant analysis were statistically significant and allowed to emphasize several structure coefficients (SC). In close games (final score differences below 9 points), the discriminant variables were the turnovers (SC = -0.47) and the assists (SC = 0.33). In balanced games (final score differences between 10 and 29 points), the variables that discriminated between the groups were the successful 2-point field-goals (SC = -0.34) and defensive rebounds (SC = -0. 36); and in unbalanced games (final score differences above 30 points) the variables that best discriminated both groups were the successful 2-point field-goals (SC = 0.37). These results allowed understanding that these players'' specific characteristics result in a different game-related statistical profile and helped to point out the importance of the perceptive and decision making process in practice and in competition.

Key points

• The players'' game-related statistical profile varied according to game type, game outcome and in formative categories in basketball.
• The results of this work help to point out the different player''s performance described in U-16 men''s basketball teams compared with senior and professional men''s basketball teams.
• The results obtained enhance the importance of the perceptive and decision making process in practice and in competition.

Key words: Basketball, game-statistics, notational analysis, winners, losers     

Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression

The present study investigated the time-course for aging-associated effects on contractile and relaxing vascular responses and nitric oxide (NO) production in the aorta from female senescence-accelerated resistant (SAMR1) and prone (SAMP8) mice. Both SAMR1 and SAMP8 were studied at three different ages: 3 (young), 6 (middle age) and 10 (old) months. Concentration–response curves to phenylephrine (10^− 8 to 10^− 5 M) or acetylcholine (10^− 9 to 10^− 5 M) were performed in the aortic rings in the absence or in the presence of NO synthase (NOS) inhibitor L-NAME (10^− 4 M). Protein and gene expression for endothelial NOS (eNOS) was determined by immunofluorescence, Western blot and real-time PCR. Although we have not seen any difference in vascular responses when comparing both strains at 3 months old, we found a significant aging-associated impairment of vascular reactivity that follows a distinct time-course in SAMR1 and SAMP8. In SAMR1, increases in phenylephrine contraction and decreases in acetylcholine relaxation were only seen at 10 months old, while SAMP8 displays altered responses at 6 months that are further impaired at 10 months old. L-NAME treatment enhanced phenylephrine contractions and completely inhibited acetylcholine relaxations in all age groups of SAMR1 and SAMP8. However, the magnitude of increase in phenylephrine contraction by L-NAME was markedly reduced by aging and followed a faster pace in SAMP8. Similar pattern of responses was observed in the time course for changes of eNOS expression, suggesting an earlier and more pronounced aging-associated decrease of NO production and eNOS expression in SAMP8. These results reveal that aging enhances contractile responses to phenylephrine and decreases endothelium-dependent relaxation to acetylcholine in the aorta from female mice by a mechanism that involves a decrease of NO production. This process occurs earlier in the aorta from SAMP8 mice, establishing these mice as suitable model to study cardiovascular aging in a convenient and standard time course.     

Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals

Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B–Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB.Greatwall was originally identified in Drosophila as a modulator of Polo activity and a protein required for DNA condensation and normal progression through mitosis (1–4). Biochemical assays in Xenopus extracts have demonstrated that Greatwall is able to inhibit PP2A–B55 phosphatase complexes by phosphorylating the cAMP-regulated phosphoprotein Arpp19 and α-endosulfine, thus participating in the maintenance of the mitotic state (5–8). The control of PP2A through the Greatwall-dependent phosphorylation of Arpp19/Ensa proteins has also been supported by genetic studies in Drosophila (9, 10). The mammalian ortholog of Greatwall, also known as microtubule-associated serine/threonine kinase-like protein (Mastl), also participates in the maintenance of the mitotic state by inhibiting PP2A phosphatases (11, 12). Inhibition of Greatwall is required for the activation of PP2A–B55α,δ complexes during mitotic exit (13), thus suggesting the relevance of this pathway in maintaining the mitotic state (4). How Greatwall activity and function is regulated is not well established. Several evidences support a role for cyclin-dependent kinase (Cdk)-dependent phosphorylation in the activation of Greatwall, and several phosphorylation sites for multiple kinases have been mapped (14, 15). In addition, although Greatwall is mostly nuclear in interphase (3, 11), the cellular and molecular basis of the control of its dynamic intracellular trafficking and its activity remains largely unknown.We show in this work that the murine Greatwall ortholog, encoded by the Mastl gene, is essential for mouse development and cell cycle progression. Greatwall-null cultures, however, display normal kinetics during the G₂/M transition, suggesting that this protein is not required for mitotic entry. Greatwall is exported to the cytoplasm before nuclear envelope breakdown (NEB) but, interestingly, this export follows nuclear import of cyclin B–Cdk1. The lack of Greatwall activity results in defects in chromosome condensation after NEB, and these defects can be rescued by concomitant ablation of B55 proteins. Our results imply that cells are subjected to a mitotic stress resulting from NEB, a moment in which nuclear chromatin becomes exposed to cytoplasmic phosphatases. We therefore propose that Greatwall shuttles to the cytoplasm before NEB and prevents mitotic collapse by inhibiting the PP2A–B55-dependent dephosphorylation of Cdk substrates.     

Significant Differences in the Interleukin-1ß and Interleukin-1 Receptor Antagonist Gene Polymorphisms in a Hungarian Population with Inflammatory Bowel Disease

Background: There is growing evidence of the importance of genetic predisposition and the activation of the mucosal immune system in the pathogenesis of inflammatory bowel disease. Thus, genes involved in the regulation of inflammation are receiving increased attention. We have studied whether Crohn's disease (CD) or ulcerative colitis (UC) is associated with certain allelic combinations of IL1B/IL1RA gene polymorphisms in a different European population than the ones studied so far. Methods: Ninety-six patients with UC, 97 with CD, and 132 healthy individuals (HC) were typed for the polymorphic regions in exon 5 of the IL1B gene and in intron 2 of the IL1RA gene, using polymerase chain reaction-based methods. Results: In CD homozygotes for allele 1 in IL1B gene polymorphism were more often present (72% versus 28%; P = 0.01) in the subgroup of patients carrying at least one copy of allele 2 in IL1RA gene polymorphism. This association was not found in HC (HC versus CD; P = 0.03) or UC. However, in UC patients with pancolitis a similar trend was observed (75% versus 25%). Several genotype combinations characterized by the presence of allele 2 of the IL1RA gene polymorphism were more common in CD (P = 0.001) and UC (P = 0.049) than in HC. Conclusions: Our data support the concept that CD and severe UC have a genetic disequilibrium in the distribution of IL1B and IL1RA gene polymorphisms. These findings together with functional studies will contribute to the understanding of the pathogenesis of the chronicity of inflammation in these diseases.     

Profile of polymorphisms of drug-metabolising enzymes and the risk of therapy-related leukaemia

Therapy-related acute myeloid leukaemia/myelodysplastic syndrome (t-AML/t-MDS) results from an impaired ability to detoxify chemotherapeutic drugs or repair drug-induced genetic damage caused by genetic polymorphisms in enzymes involved in the metabolism of drugs. We analysed the prevalence of genetic polymorphisms of CYP1A1*2A(T6235C), CYP2E1*5B(C-1019T), CYP3A4*1B(A-290G), del{GSTT1}, del{GSTM1}, NQO1*2(C609T), MTHFR(C677T) and TYMS 2R/3R in 78 t-AML/t-MDS and 458 normal individuals (control group, CG) using real-time and conventional polymerase chain reaction (PCR)-based methods. The incidences of polymorphisms among t-AML/t-MDS patients and CG individuals were similar. However, a polymorphism profile consisting of CYP1A1*2A, del{GSTT1} and NQO1*2 strongly modified the risk of t-AML/t-MDS. The absence of all three polymorphisms decreased the risk of t-AML/t-MDS 18-fold (odds ratio (OR) = 0.054, 95% confidence interval (CI) = 0.005-0.63, P = 0.02), whereas the presence of only NQO1*2 or all three polymorphisms enhanced the risk of t-AML/t-MDS (OR = 2.09, 95% CI = 1.08-4.03, P = 0.03 and OR = 18.42, 95% CI = 1.59-212.76, P = 0.02 respectively). Thus, the profiles of genetic polymorphisms of drug-metabolising enzymes might explain the increased risk to t-AML/t-MDS observed in some patients treated with polychemotherapy.     

Cutaneous metastases in renal cell carcinoma

Cutaneous metastases from a renal cell carcinoma are rarely diagnosed during life. We report a case of renal carcinoma metastatic to the skin that occurred 18 months after kidney removal. The cutaneous metastasis was excised. Cutaneous metastases from urological tumors are uncommon and occur in 1% of the patients, and their clinical appearance may mimic other common dermatological disorders affecting patients with advanced malignancies.     

Immunohumoral response during laparoscopic and open living donor nephrectomy: an experimental model

Measurement of interleukins (IL) and C-reactive protein (CRP) have demonstrated that a laparoscopic approach may induce less surgical stress than an open approach. The potential influence of this observation in living donor nephrectomy has scarcely been analyzed. The aim of the study was to analyze the immunohumoral response induced by laparoscopic versus open donor nephrectomy in an experimental model. Twenty pigs underwent left nephrectomy, 10 by laparoscopy and 10 by an open approach. In both groups the following parameters were measured: CRP, IL-2, IL-10, tumour necrosis factor alpha (TNF alpha), and endothelin-1 (ET-1). The determinations were done at different times: basal, immediately as well as on the first, third, fifth, and seventh days after the procedure. A comparative analysis between groups demonstrated a significant increases among the open group in the following markers: CRP (1.44 +/- 0.88 vs 1.32 +/- 0.14 mg/dL, P = .046); TNF alpha (131.14 +/- 41.37 vs 57.19 +/- 23.71 pg/mL; P > .001); and ET-1 (0.91 +/- 0.49 vs 0.56 +/- 0.5 fmol/mL; P = .001). The laparoscopic group showed higher levels of IL-2 than the open group. In conclusion, open donor nephrectomy produced a greater immunohumoral response than a laparoscopic approach. The influence of these observations on ischemia-reperfusion injury or on immediate graft function after kidney transplantation has not been clearly established.     

Comparative analysis of the hemodynamic and respiratory parameters during laparoscopic versus open living donor nephrectomy: an experimental model

Increased intrabdominal pressure induced by pneumoperitoneum induces modifications in cardiovascular and respiratory systems. The aim of the study was to analyze the hemodynamic and respiratory modifications produced by pneumoperitoneum during living donor nephrectomy in a porcine experimental model. Twenty pigs underwent left nephrectomy, 10 by laparoscopy and 10 by an open approach. The following parameters were measured: mean arterial pressure (MAP), central venous pressure, cardiac output (CO), systemic vascular resistance (SVR), end tidal CO2 (ETCO2), minute volume (MV), respiratory airway pressure (RAP), and "compliance." Both groups were monitored for cardiac and respiratory systems at basal, 5, 30, and 60 minutes as well as postsurgery. The comparative analysis demonstrated increased CO with a higher difference at 30 minutes (4.33 +/- 0.73 vs 8.54 +/- 1.26 L/min, P < .001); decreased SVR (1118.81 +/- 302.52 vs 663.37 +/- 81.45 dinas x s x cm(-5), P < .001), and elevated MAP among the laparoscopic group (66.5 +/- 11.52 vs 80.25 +/- 2.49 mm Hg, P = .004). Analysis of respiratory modifications showed an initial increase in ETCO2 (44.3 +/- 2.6 vs 54.1 +/- 12.56 mm Hg, P < .035) and a higher MV administered (5.6 +/- 0.1 vs 7.01 +/- 0.96 L/min, P = .03) to the laparoscopy group. An increased RAP was observed at 5 minutes (22.11 +/- 2.76 vs 28.8 +/- 3.68 mm Hg, P < .001), in the laparoscopic group and lower levels of "compliance" at the same moment in that group (16 +/- 1.66 vs 14.9 +/- 4.07 cm H2O). Laparoscopic nephrectomy caused an increase in CO and MAP and decreased SVR. Likewise there were elevations of RAP, ETCO2, and MV and a slight decrease in the "compliance."     

Mycophenolate mofetil levels in stable kidney transplant recipients

The usefulness of mycophenolate mofetil (MMF) levels in stable kidney transplant patients is not well known. We measured MMF trough levels in 137 adult kidney recipients with more than 1 year of stable graft function. The MMF dose was adjusted according to hematological or gastrointestinal toxicity, it was 500 mg in 22 (16%) patients; 750 mg in 22 (16%); 1000 mg in 69 (50.5%); 1500 mg in 15 (11%); and 2000 mg in 9 (6.5%). We analyzed the total dose, virgule dose/kg, and MMF levels in relation to efficacy parameters (creatinine, proteinuria) and hematological toxicity (erythrocytes, leukocytes, and platelets) at the time of MMF level determinations and 3 months thereafter. Statistical analyses were performed with SSPS 12.0, including sensitivity and specificity analyses by ROC. Mean MMF levels were 3.68 mg/L (Pc25, 1.6-Pc75, 4.4 mg/L) with significant differences according to dose (P < .001). Trough MMF levels did not have discriminatory capacity in the area under the ROC for anemia, renal failure, or proteinuria at the time of determination or 3 months later. The percentage of patients without proteinuria was high among patients with MMF levels between 1.6 and 4.4 mg/L. The MMF levels were low in patients who had a major increase in creatinine (1.6 vs 3.8 mg/L, P < .05). In stable renal transplant patients the levels of MMF were related to the administered dose, and they are higher than those previously described in patients with less than a year follow-up with a functioning kidney. They did not have discriminatory value at the time of determination or 3 months later. Nevertheless, low MMF levels could help recognize patients at risk of developing chronic nephropathy.