Profile of thrombin generation in children with acute lymphoblastic leukemia treated by Berlin-Frankfurt-Münster (BFM) protocols

Treatment with L-asparaginase is associated with coagulation disturbances with deep venous thrombosis being the most common clinical consequence. Use of the calibrated automated thrombogram allows precise estimation of thrombin generated in vitro. We show the first data on thrombin generation, measured by calibrated automated thrombography (CAT), in children with acute lymphoblastic leukemia treated with L-asparaginase. Thrombin generation was measured by means of CAT in 23 children treated for acute lymphoblastic leukemia. Samples were obtained at predefined time points during the induction and reinduction phase of acute lymphoblastic leukemia-intercontinental Berlin-Frankfurt-Münster (BFM) 2000 or Associazione Italiana Ematologica Oncologia Pedaitrica Interim BFM 2000 protocols. Antihrombin and fibrinogen were measured on the same sample. Twenty-eight sets of thrombin generation measurements were collected from 23 patients. We observed no significant effect of antithrombin deficiency and/or hypofibrinogenemia on thrombin generation. Endogenous thrombin generation and peak thrombin were significantly higher during induction than in the reinduction phase (P?相似文献   

Systems Biology and Biomechanical Model of Heart Failure

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.     

Role of orthoptics and scoring system for orbital floor blowout fracture: surgical or conservative treatment

AIM: To assess the role of orthoptics in referring patients with orbital floor blowout fracture (OFBF) for conservative or surgical treatment and based on the results, to propose a scoring system for such decision making. METHODS: A retrospective analysis of 69 patients with OFBF was performed (35 treated conservatively, 34 surgically). The role of orthoptics in referring to surgery or conservative treatment was retrospectively evaluated, the factors with the highest significance for decision making were identified, and a scoring system proposed using Logistic regression. RESULTS: According to defined criteria, the treatment was unsuccessful in 2 (6%) surgically treated and only in one (3%) conservatively treated patient. The proposed scoring system includes the defect size and several values resulting from the orthoptic examination, the elevation of the eyebulb measured on Lancaster screen being the most significant. CONCLUSION: The study demonstrates the benefits of orthoptic examination when making decisions on conservative or surgical treatment and for diagnosing ocular motility disorder (with or without binocular diplopia) in OFBF patients. The proposed scoring system could, following verification in a prospective study, become a valuable adjunctive tool.     

Long-term survival of the uncemented Balgrist total hip replacement cup

Purpose

The purpose of this study was to evaluate the long-term clinical and radiographic outcomes of the Balgrist total hip replacement cup.

Methods

We report the results of a retrospective review of 195 total hip prostheses with Balgrist cup implanted in 178 patients. There were 59 men and 119 women with a mean age at surgery of 52.3 years (range, 19–72). Cox regression was used to determine the influence of independent variables on the survivorship of the prosthesis.

Results

There were 117 (66 %) of 178 patients, and 131 (67 %) of 195 hips available for assessment at a mean follow-up of 17.4 years. A total of 21 patients (22 hips) were lost from follow-up (12 %). A total of 25 patients (27 hips) required some type of re-operation during the follow-up period. Eight of 27 re-operations (30 %) were directly caused by the Balgrist cup failure due to fatigue fracture of the metallic shell (n = 5; 19 %), polyethylene wear (n = 2; 7 %) and aseptic loosening (n = 1; 4 %). The mean polyethylene wear rate was 0.068 mm/year (range, 0.008–0.230; SD = 0.043). The risk of re-operation for any reason was decreased with dysplastic hip as a primary diagnosis (hazard ratio; HR = 0.250; 95 % CI 0.086–0.725) and with greater age at the time of surgery (HR = 0.923; 95 % CI 0.880–0.969). The 19-year survivorship with re-operation for any reason was 75.6 % (95 % CI 67.0–84.2). The 19-year survivorship with re-operation for the Balgrist cup failure was 90.5 % (95 % CI 83.4–97.6).

Conclusions

The Balgrist cup continues to provide excellent clinical and radiological outcomes. This is associated at least in part with a low polyethylene wear rate. The main reason for the Balgrist cup failure is fatigue fracture of the metallic shell.     

Discriminating value of total minor physical anomaly score on the Waldrop scale between patients with bipolar I disorder and normal controls

Minor physical anomalies (MPAs) are slight structural aberrations indicative of abnormal neurodevelopment. Most studies of MPAs in bipolar disorder have yielded limited results. We attempted to assess the potential value of MPAs as a classifying test in the status bipolar I patients vs. normal controls. Sixty one bipolar I patients and 103 controls were evaluated for MPAs using a slightly modified version of the Waldrop scale. The specificity, sensitivity and predictive value of different total MPA (MPA-T) scores were determined. The cut-off MPA-T scores that optimally discriminated patients from controls (exhibiting the most balanced sets of sensitivity, specificity, positive and negative predictive values) were MPA-T≥4 and MPA-T≥5. These values set a “border zone” in which bipolar I patients began to prevail significantly over controls. The latter presented most frequently with MPA-T ≤3 and rarely with MPA-T ≥6. Bipolar I patients prevailed among outliers (subjects with significantly higher MPA-T scores). Our data establish MPA-T score as a reliable index in distinguishing between bipolar I patients and normal controls and are consistent with the hypothesis of abnormal neurodevelopment in bipolar disorder.     

Neonatal lipopolysaccharide treatment has long‐term effects on monoaminergic and cannabinoid receptors in the rat

Brain inflammation in early life has been proposed to play important roles in the development of anxiety and psychosis‐related behaviors in adulthood, behaviors that rely on the integrity of dopamine and/or serotonin systems. Moreover recent behavioral and anatomical evidence suggests involvement of CB1 receptors in the control of emotion and mood. In this study, we determined the effects of neonatal LPS treatment on dopamine, serotonin, and cannabinoid receptor binding in adulthood. Rats were treated with the bacterial endotoxin lipopolysaccharide (LPS) on postnatal day (PND) 3 and 5. Dopamine D1, D2, serotonin 5HT1A, 5HT2A, and serotonin transporter and cannabinoid CB1 receptor binding across several brain regions were measured autoradiographically in adulthood (PND 85). Neonatal LPS treatment caused a significant increase in dopamine D2 in the nucleus accumbens and olfactory tubercle, a decrease in 5HT1A receptor binding in the hippocampus CA1 and ventromedial hypothalamus. A decrease in CB1 receptor binding after neonatal LPS was observed in the amygdala. Neonatal LPS had no significant impact on dopamine D1, serotonin 5HT2A or serotonin transporter binding in any of the brain regions examined. Our results suggest long lasting, region specific effects and differential impact on dopamine, serotonin and cannabinoid receptor systems following neonatal inflammation, that may form the basis for compromised anxiety and psychosis related behaviors. Synapse, 2013. © 2013 Wiley Periodicals, Inc.     

Bone Mass and Strength in School‐Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study

Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school‐age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole‐body and hip scans were measured using the same densitometer (GE‐Lunar iDXA) at a mean age of 6.2 years. Hip dual‐energy X‐ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole‐body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre‐ and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research.