Atraumatic splenic rupture in amyloidosis

BACKGROUND: Splenic involvement in amyloidosis is rather frequent (5-10%). An atraumatic rupture of the affected spleen is however an extremely rare event. We report on a patient with undiagnosed amyloidosis who underwent emergency splenectomy for atraumatic splenic rupture. METHODS: Review of the literature and identification of 31 patients, including our own case report, with atraumatic splenic rupture in amyloidosis. Analysis of the clinical presentation, the surgical management, the nomenclature and definition of predisposing factors of splenic rupture. RESULTS: We identified 15 women and 16 men (mean age 53.3 +/- 12.4 years; median 52, range: 27-82 years) with an atraumatic splenic rupture. Easy skin bruisability and factor X deficiency were detected in four (13%) and five patients (16%), respectively. The diagnosis of splenic rupture was made either by computed tomography (n = 12), ultrasound (n = 5), exploratory laparotomy (n = 9) or autopsy (n = 4). All patients underwent surgery (n = 27) or autopsy (n = 4). Amyloidosis was previously diagnosed in nine patients (29%). In the remaining 22 patients (71%), the atraumatic splenic rupture represented the initial manifestation of amyloidosis. Twenty-five patients (81%) suffered from primary (AL) and four patients (13%) from secondary amyloidosis (AA). In two patients, the type of amyloidosis was not specified. A moderate splenomegaly was a common feature (68%) and the characteristic intraoperative finding was an extended subcapsular hematoma with a limited parenchymal laceration (65%). In five patients with known amyloidosis, the atraumatic splenic rupture was closely associated with autologous stem-cell transplantation (ASCT) (16%). Three patients were suffering from multiple myeloma (10%). A biopsy-proven amyloidotic liver involvement was present in 14 patients (45%), which lead to atraumatic liver rupture in two patients. The splenic rupture related 30-day mortality was 26% (8/31). CONCLUSIONS: Atraumatic splenic rupture in amyloidosis is associated with a high 30-day mortality. It occurs predominantly in patients with previously undiagnosed amyloidosis. A moderate splenomegaly, coagulation abnormalities (easy skin bruisability, factor X deficiency) and treatment of amyloidosis with ASCT are considered predisposing factors for an atraumatic splenic rupture.

Lifestyle and stroke risk: a review

PURPOSE OF REVIEW: In recent years, many epidemiological studies have given new insights into old and new lifestyle factors that influence the risk of cerebrovascular events. In this review, we refer to the most important articles to highlight recent advances, especially those important for stroke prevention. RECENT FINDINGS: This review focuses on the most recent studies that show the association of environmental factors, nutrition, alcohol, tobacco, education, lifestyle and behavior with the risk of vascular disease, including ischemic stroke and cerebral hemorrhage. The link between air pollution and stroke risk has become evident. Low education levels and depression are established as risk factors. This is also true for heavy alcohol consumption, although moderate drinking may be protective. Active and passive smoking are independent risk factors, and a smoking ban in public places has already reduced cardiovascular events in the short term. Physical activity reduces stroke risk; overweight increases it. However, clinical trials to assess the effect of weight reduction on stroke risk are still lacking. Fruits, vegetables, fish, fibers, low-fat dairy products, potassium and low sodium consumption are known and recommended to reduce cardiovascular risk. Data on omega 3 fatty acid, folic acid and B vitamins are inconsistent, and antioxidants are not recommended. SUMMARY: Stroke can be substantially reduced by an active lifestyle, cessation of smoking and a healthy diet. Both public and professional education should promote the awareness that a healthy lifestyle and nutrition have the potential to reduce the burden of stroke.

Characterization of apxIVA, a new RTX determinant of Actinobacillus pleuropneumoniae

A fourth type of RTX determinant was identified in Actinobacillus pleuropneumoniae and was designated apxIVA. When expressed in Escherichia coli, recombinant ApxIVA showed a weak haemolytic activity and co-haemolytic synergy with the sphingomyelinase (beta-toxin) of Staphylococcus aureus. These activities required the presence of an additional gene, ORF1, that is located immediately upstream of apxIVA. The apxIVA gene product could not be detected in A. pleuropneumoniae cultures grown under various conditions in vitro; however, pigs experimentally infected with A. pleuropneumoniae serotypes 1, 5 and 7 started to produce antibodies that reacted with recombinant ApxIVA 14 d post-infection, indicating that apxIVA is expressed in vivo. In addition, sera from pigs naturally and experimentally infected with any of the serotypes all reacted with recombinant ApxIVA. The apxIVA gene from the serotype 1 A. pleuropneumoniae type strain Shope 4074T encodes a protein with a predicted molecular mass of 202 kDa which has typical features of RTX proteins including hydrophobic domains in the N-terminal half and 24 glycine-rich nonapeptides in the C-terminal half that bind Ca2+. The glycine-rich nonapeptides are arranged in a modular structure and there is some variability in the number of modules in the ApxIVA proteins of different serotypes of A. pleuropneumoniae. The deduced amino acid sequences of the ApxIVA proteins have significant similarity with the Neisseria meningitidis iron-regulated RTX proteins FrpA and FrpC, and to a much lesser extent with other RTX proteins. The apxIVA gene could be detected in all A. pleuropneumoniae serotypes and seems to be species-specific. Although the precise role of this new RTX determinant in pathogenesis of porcine pleuropneumonia needs to be determined, apxIVA is the first in vivo induced toxin gene that has been described in A. pleuropneumoniae.

Intracellular localization of the BCL-2 family member BOK and functional implications

The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a 'tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.

Human intervertebral disc stiffness correlates better with the Otsu threshold computed from axial T2 map of its posterior annulus fibrosus than with clinical classifications

Degeneration of the intervertebral disc, sometimes associated with low back pain and abnormal spinal motions, represents a major health issue with high costs. A non-invasive degeneration assessment via qualitative or quantitative MRI (magnetic resonance imaging) is possible, yet, no relation between mechanical properties and T2 maps of the intervertebral disc (IVD) has been considered, albeit T2 relaxation time values quantify the degree of degeneration. Therefore, MRI scans and mechanical tests were performed on 14 human lumbar intervertebral segments freed from posterior elements and all soft tissues excluding the IVD. Degeneration was evaluated in each specimen using morphological criteria, qualitative T2 weighted images and quantitative axial T2 map data and stiffness was calculated from the load-deflection curves of in vitro compression, torsion, lateral bending and flexion/extension tests. In addition to mean T2, the OTSU threshold of T2 (TOTSU), a robust and automatic histogram-based method that computes the optimal threshold maximizing the distinction of two classes of values, was calculated for anterior, posterior, left and right regions of each annulus fibrosus (AF). While mean T2 and degeneration schemes were not related to the IVDs' mechanical properties, TOTSU computed in the posterior AF correlated significantly with those classifications as well as with all stiffness values. TOTSU should therefore be included in future degeneration grading schemes.

DXA predictions of human femoral mechanical properties depend on the load configuration

The aim of this study was to evaluate the ability of dual energy X-rays absorptiometry (DXA) areal bone mineral density (aBMD) measured in different regions of the proximal part of the human femur for predicting the mechanical properties of matched proximal femora tested in two different loading configurations. 36 pairs of fresh frozen femora were DXA scanned and tested until failure in two loading configurations: a fall on the side or a one-legged standing. The ability of the DXA output from four different regions of the proximal femur in predicting the femoral mechanical properties was measured and compared for the two loading scenarios. The femoral neck DXA BMD was best correlated to the femoral ultimate force for both configurations and predicted significantly better femoral failure load (R2=0.80 vs. R2=0.66, P<0.05) when simulating a side than when simulating a standing configuration. Conversely, the work to failure was predicted similarly for both loading configurations (R2=0.54 vs. R2=0.53, P>0.05). Therefore, neck BMD should be considered as one of the key factors for discriminating femoral fracture risk in vivo. Moreover, the better predictive ability of neck BMD for femoral strength if tested in a fall compared to a one-legged stance configuration suggests that DXA's clinical relevance may not be as high for spontaneous femoral fractures than for fractures associated to a fall.