Advanced age increases the failure rate of non-operative management of blunt splenic injuries

Introduction: Non-operative management (NOM) of blunt splenic injuries in hemodynamically stable patients is nowadays considered the standard treatment. Material and Methods: The aim was to clarify the criteria used for primary operative management (OM) and planned NOM. Furthermore, the study aimed to identify risk factors for failure of NOM. All adult patients with blunt splenic injuries treated from 2000-2008 were reviewed and a logistic regression analysis employed. Results: There were 206 patients (146 men, 70.9%). Mean age was 38.2 ± 19.1 years. The mean Injury Severity Score (ISS) was 30.9 ± 11.6. The American Association for the Surgery of Trauma (AAST) classification of the splenic injury was: grade I, n = 43 (20.9%); grade II, n = 52 (25.2%); grade III, n = 60 (29.1%), grade IV, n = 42 (20.4%) and grade V, n = 9 (4.4%). 47 patients (22.8%) required immediate surgery (OM). More than 5 units of red cell transfusions (odds ratio [OR] 13.72, P < 0.001), a Glasgow Coma Scale < 11 (OR 9.88, P = 0.009) and age ? 55 years (OR 3.29, P = 0.038) were associated with primary OM. 159 patients (77.2%) qualified for a non-surgical approach (NOM), which was successful in 89.9% (143/159). The overall splenic salvage rate amounted to 69.4% (143/206). Multiple logistic regression analysis found age ? 40 years to be the only factor significantly and independently related to the failure of NOM (OR 13.58, P = 0.001). Conclusion: Advanced age is associated with an increased failure rate of NOM in patients with blunt splenic injuries.

Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination.

BACKGROUND: Brain inflammation plays a central role in numerous brain pathologies, including multiple sclerosis (MS). Microglial cells and astrocytes are the effector cells of neuroinflammation. They can be activated also by agents such as interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Peroxisome proliferator-associated receptor (PPAR) pathways are involved in the control of the inflammatory processes, and PPAR-beta seems to play an important role in the regulation of central inflammation. In addition, PPAR-beta agonists were shown to have trophic effects on oligodendrocytes in vitro, and to confer partial protection in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the present work, a three-dimensional brain cell culture system was used as in vitro model to study antibody-induced demyelination and inflammatory responses. GW 501516, a specific PPAR-beta agonist, was examined for its capacity to protect from antibody-mediated demyelination and to prevent inflammatory responses induced by IFN-gamma and LPS. METHODS: Aggregating brain cells cultures were prepared from embryonal rat brain, and used to study the inflammatory responses triggered by IFN-gamma and LPS and by antibody-mediated demyelination induced by antibodies directed against myelin-oligodendrocyte glycoprotein (MOG). The effects of GW 501516 on cellular responses were characterized by the quantification of the mRNA expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), inducible NO synthase (i-NOS), PPAR-beta, PPAR-gamma, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and high molecular weight neurofilament protein (NF-H). GFAP expression was also examined by immunocytochemistry, and microglial cells were visualized by isolectin B4 (IB4) and ED1 labeling. RESULTS: GW 501516 decreased the IFN-gamma-induced up-regulation of TNF-alpha and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-beta agonist. However, it increased IL-6 m-RNA expression. In demyelinating cultures, reactivity of both microglial cells and astrocytes was observed, while the expression of the inflammatory cytokines and iNOS remained unaffected. Furthermore, GW 501516 did not protect against the demyelination-induced changes in gene expression. CONCLUSION: Although GW 501516 showed anti-inflammatory activity, it did not protect against antibody-mediated demyelination. This suggests that the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes.

The efficacy of pharmacotherapy for decreasing the expansion rate of abdominal aortic aneurysms: a systematic review and meta-analysis.

BACKGROUND: Pharmacotherapy may represent a potential means to limit the expansion rate of abdominal aortic aneurysms (AAAs). Studies evaluating the efficacy of different pharmacological agents to slow down human AAA-expansion rates have been performed, but they have never been systematically reviewed or summarized. METHODS AND FINDINGS: Two independent reviewers identified studies and selected randomized trials and prospective cohort studies comparing the growth rate of AAA in patients with pharmacotherapy vs. no pharmacotherapy. We extracted information on study interventions, baseline characteristics, methodological quality, and AAA growth rate differences (in mm/year). Fourteen prospective studies met eligibility criteria. Five cohort studies raised the possibility of benefit of beta-blockers [pooled growth rate difference: -0.62 mm/year, (95%CI, -1.00 to -0.24)], but this was not confirmed in three beta-blocker RCTs [pooled RCT growth rate difference: -0.05 mm/year (-0.16 to 0.05)]. Statins have been evaluated in two cohort studies that yield a pooled growth rate difference of -2.97 (-5.83 to -0.11). Doxycycline and roxithromycin have been evaluated in two RCTs that suggest possible benefit [pooled RCT growth rate difference: -1.32 mm/year (-2.89 to 0.25)]. Studies assessing NSAIDs, diuretics, calcium channel blockers and ACE inhibitors, meanwhile, did not find statistically significant differences. CONCLUSIONS: Beta-blockers do not appear to significantly reduce the growth rate of AAAs. Statins and other anti-inflammatory agents appear to hold promise for decreasing the expansion rate of AAA, but need further evaluation before definitive recommendations can be made.

Impact of preoperative embolization of the left gastric artery on the rate of anastomotic leakage after esophageal resection

Objective: Impaired blood flow of the gastric tube represents a major cause of anastomotic leakage after esophageal resection. In order to improve local vascularisation, preoperative embolization (PE) of the left gastric artery has recently been proposed. The aimof this study was to assess our initial experience of this novel approach with a particular focus on anastomotic leakage.Methods: A consecutive series of 102 patients (81 male, 21 female, median age 64 years) underwent resection (82 Ivor-Lewis procedures, 9 transhiatal resections, 11 triple incisions) for esophageal malignancies at our institution from 2000 to 2009. Since 2004, PE was used selectively in 19 patients 21 days prior to elective esophagectomy. Selection criteria were normal gastric vascular anatomy, no pre-existing vascular disease, i.e. atheromatosis of the celiac trunk or superior mesenteric artery, and resectability of the tumor. PE was performed under local anesthesia on a dedicated system in a standard fashion. Following percutaneous transfemoral visceral angiography to identify gastric vascular anatomy, embolization was performed either with 5-F or with coaxial 3-F catheters and fibered metal coils. We analyzed retrospectively patient's data, operative data, and outcome from a prospective database.Results: The overall anastomotic leakage rate was 18・6% (19/102 patients); cervical anastomosis had a leak rate of 25% compared to intrathoracic anastomosis leak rate of 18・2%. While 17 of 83 patients without PE developed anastomotic leakage (20・5%), there were only 2 of 19 patients after PE revealing an anastomotic leakage (10・5%). Otherwise, patients with PE had no more other complications. There was only one PE-related complication (i.e. partial splenic necrosis).Mean hospital stay was 25 days versus 27 days for patients with PE and without PE, respectively. The mortality rate was 7・8% (8/102 patients), whereby four deaths were related to anastomotic leakage (1 and 3 patients with PE and without PE, respectively).Conclusion: PE is an interesting novel approach to improve gastric blood flow in order to minimize anastomotic leakage. Its application is safe and technically easy. Our preliminary experience revealed a decrease of the anastomotic leakage rate of almost 50%.

The limits of brain determinacy.

The genes do not control everything that happens in a cell or an organism, because thermally induced molecular movements and conformation changes are beyond genetic control. The importance of uncontrolled events has been argued from the differences between isogenic organisms reared in virtually identical environments, but these might alternatively be attributed to subtle, undetected differences in the environment. The present review focuses on the uncontrolled events themselves in the context of the developing brain. These are considered at cellular and circuit levels because even if cellular physiology was perfectly controlled by the genes (which it is not), the interactions between different cells might still be uncoordinated. A further complication is that the brain contains mechanisms that buffer noise and others that amplify it. The final resultant of the battle between these contrary mechanisms is that developmental stochasticity is sufficiently low to make neurobehavioural defects uncommon, but a chance component of neural development remains. Thus, our brains and behaviour are not entirely determined by a combination of genes-plus-environment.

A fully-automatic caudate nucleus segmentation of brain MRI: application in volumetric analysis of pediatric attention-deficit/hyperactivity disorder

Background Accurate automatic segmentation of the caudate nucleus in magnetic resonance images (MRI) of the brain is of great interest in the analysis of developmental disorders. Segmentation methods based on a single atlas or on multiple atlases have been shown to suitably localize caudate structure. However, the atlas prior information may not represent the structure of interest correctly. It may therefore be useful to introduce a more flexible technique for accurate segmentations. Method We present Cau-dateCut: a new fully-automatic method of segmenting the caudate nucleus in MRI. CaudateCut combines an atlas-based segmentation strategy with the Graph Cut energy-minimization framework. We adapt the Graph Cut model to make it suitable for segmenting small, low-contrast structures, such as the caudate nucleus, by defining new energy function data and boundary potentials. In particular, we exploit information concerning the intensity and geometry, and we add supervised energies based on contextual brain structures. Furthermore, we reinforce boundary detection using a new multi-scale edgeness measure. Results We apply the novel CaudateCut method to the segmentation of the caudate nucleus to a new set of 39 pediatric attention-deficit/hyperactivity disorder (ADHD) patients and 40 control children, as well as to a public database of 18 subjects. We evaluate the quality of the segmentation using several volumetric and voxel by voxel measures. Our results show improved performance in terms of segmentation compared to state-of-the-art approaches, obtaining a mean overlap of 80.75%. Moreover, we present a quantitative volumetric analysis of caudate abnormalities in pediatric ADHD, the results of which show strong correlation with expert manual analysis. Conclusion CaudateCut generates segmentation results that are comparable to gold-standard segmentations and which are reliable in the analysis of differentiating neuroanatomical abnormalities between healthy controls and pediatric ADHD.

Prices of medicines: a case-study on the impact of the rate-of-return regulation in the United Kingdom

This work carries out an empirical evaluation of the impact of the main mechanism for regulating the prices of medicines in the UK on a variety ofpharmaceutical price indices. The empirical evidence shows that the overall impact of the rate of return cap appears to have been slight or even null, and in any case that the impact would differ across therapeutic areas. These empiricalfindings suggest that the price regulation has managed to encourage UK-based firms¿ diversification in many therapeutic areas

Growth rate of fractal copper electrodeposits: Potential and concentration effects

Experiments are reported on fractal copper electrodeposits. An electrochemical cell was designed in order to obtain a potentiostatic control on the quasi-two-dimensional electrodeposition process. The aim was focused on the analysis of the growth rate of the electrodeposited phase, in particular its dependence on the electrode potential and electrolyte concentration.

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

OBJECTIVE: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS: We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION: According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

Role of brain alpha 1B-adrenoceptors in modafinil-induced behavioral activity.

These studies show that either central pharmacological blockade or genetic ablation of alpha(1B)-adrenoceptors markedly attenuates the behavioral activation caused by modafinil, implicating these receptors in the drug's action.

Effect of low-dose chest irradiation before chemotherapy on the rate of local failure in small-cell lung cancer.

PURPOSE: To evaluate the rate of tumor recurrence within the irradiated volume after initial low-dose irradiation of limited-stage small-cell lung cancer (SCLC), to assess the tolerance of a sequential combination of low-dose chest irradiation followed by chemotherapy, and to confirm the responsiveness of limited-stage SCLC to low-dose irradiation. METHODS AND MATERIALS: In this pilot study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin, doxorubicin, and etoposide for six cycles). RESULTS: We present our final results with a median follow-up of surviving patients of 7 years. The response rate to this low-dose irradiation was 83%, with an overall response rate to radiochemotherapy of 96% and a median survival of 21 months. No unexpected early or late toxicity was observed. The rate of initial isolated local failure was 8%, which compares favorably with other published series using higher doses of radiochemotherapy. CONCLUSION: An initial chest irradiation of 20 Gy before chemotherapy could be sufficient to reduce the risk of local failure during the time of survival of patients with limited-stage SCLC. Potential advantages of this treatment may be the prevention of resistance mechanisms to radiotherapy induced by preliminary chemotherapy and a reduced radiation-induced toxicity.

Clinical growth rate of acoustic schwannomas: correlation with the growth fraction as defined by the monoclonal antibody ki-67.

The growth rate of acoustic tumors, although slow, varies widely. There may be a continuous spectrum or distinct groups of tumor growth rates. Clinical, audiologic, and conventional histologic tests have failed to shed any light on this problem. Modern immunohistochemical methods may stand a better chance. The Ki-67 monoclonal antibody stains proliferating cells and is used in this study to investigate the growth fraction of 13 skull base schwannomas. The acoustic tumors can be divided into two different growth groups, one with a rate five times the other. The literature is reviewed to see if this differentiation is borne out by the radiologic studies. Distinct growth rates have been reported: one very slow, taking 50 years to reach 1 cm in diameter, a second rate with a diameter increase of 0.2 cm/year, and a third rate five times the second, with a 1.0 cm increase in diameter per year. A fourth group growing at 2.5 cm/year is postulated, but these tumors cannot be followed for long radiologically, since symptoms demand surgical intervention. The clinical implications of these separate growth rates are discussed.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications.

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

Diallel analysis for grain yield and mineral absorption rate of soybeans grown in acid brazilian savannah soil

High available aluminium and low levels of calcium below the ploughed zone of the soil are limiting factors for agricultural sustainability in the Brazilian Cerrados (Savannahs). The mineral stresses compound with dry spells effect by preventing deep root growth of cultivated plants and causes yield instability. The mode of inheritance for grain yield and mineral absorption ratio of a diallel cross in soybeans [Glycine max (L.) Merrill] grown in high and low Al areas was identified. Differences among the genotypes for grain yield were more evident in the high Al, by grouping tolerant and non-tolerant genotypes for their respective arrays in the hybrids. A large proportion of genetic variance was additive for grain yield and mineral absorption ratio in both environments. High heritability values suggest that soybeans can be improved by crosses among Al-tolerant genotypes, using modified pedigree, early generation and recurrent selection schemes.