Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial

From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.     

The complement system in central nervous system diseases

The activation of complement system is important factor in inflammatory, neurodegenerative and cerebrovascular diseases. CNS cells are able to synthesize complement components, and myelin and oligodendrocytes (OLG) are known to activate the classical pathway of complement in vitro in the absence of antibodies. Although activation of the complement system is known to promote tissue injury, recent evidence has also indicated that this process can have neuroprotective effects. In particular, terminal C5b-9 complexes enhance OLG survival both in vitro and in vivo. Complement activation may also reduce the accumulation of amyloid and degenerating neurons by promoting their clearance and suggest that certain inflammatory defense mechanisms in the brain may be beneficial in neurodegenerative disease. Complement system activation plays also an important role in brain damage after ischemic injury or head trauma. These findings strongly suggest that complement activation and membrane assembly of C5b-9 can play a role in injury but can also provide neuroprotection depending on the pathophysiological context.     

Skeletal pattern in subjects with temporomandibular joint disorders

Introduction

To establish the skeletal pattern in subjects with malocclusions and temporomandibular disorders (TMD); to assess the relationship between craniofacial skeletal structures and TMD in subjects with malocclusions.

Material and methods

Sixty-four subjects with malocclusions, over 18 years of age, were included in the study. Temporomandibular disorders were clinically assessed according to the Helkimo Anamnestic Index. Subjects underwent a lateral cephalogram. Subjects were grouped according to the sagittal skeletal pattern (ANB angle) into class I, II and III. Parametric Student tests with equal or unequal variations were used (variations were previously tested with Levene test).

Results

Twenty-four patients with TMD (experimental sample); 40 patients without TMD (control group); interincisal angle was higher in class I and II (p < 0.05) experimental subjects; overjet was larger in experimental subjects; midline shift and Wits appraisal were broader in the experimental group in all three classes. In class III subjects, the SNB angle was higher in the experimental group (p = 0.01). Joint noises followed by reduced mandible mobility, muscular pain and temporomandibular joint (TMJ) pain were the most frequent symptoms in subjects with TMD and malocclusions.

Conclusions

Temporomandibular joint status is an important factor to consider when planning orthodontic treatment in patients with severe malocclusions; midline shift, large overjet and deep overbite have been associated with signs and symptoms of TMD.     

RGC-32 regulates reactive astrocytosis and extracellular matrix deposition in experimental autoimmune encephalomyelitis

Extracellular matrix (ECM) deposition in active demyelinating multiple sclerosis (MS) lesions may impede axonal regeneration and can modify immune reactions. Response gene to complement (RGC)-32 plays an important role in the mediation of TGF-β downstream effects, but its role in gliosis has not been investigated. To gain more insight into the role played by RGC-32 in gliosis, we investigated its involvement in TGF-β-induced ECM expression and the upregulation of the reactive astrocyte markers α-smooth muscle actin (α-SMA) and nestin. In cultured neonatal rat astrocytes, collagens I, IV, and V, fibronectin, α-SMA, and nestin were significantly induced by TGF-β stimulation, and RGC-32 silencing resulted in a significant reduction in their expression. Using astrocytes isolated from RGC-32 knock-out (KO) mice, we found that the expression of TGF-β-induced collagens I, IV, and V, fibronectin, and α-SMA was significantly reduced in RGC-32 KO mice when compared with wild-type (WT) mice. SIS3 inhibition of Smad3 phosphorylation was also associated with a significant reduction in RGC-32 nuclear translocation and TGF-β-induced collagen I expression. In addition, during experimental autoimmune encephalomyelitis (EAE), RGC-32 KO mouse astrocytes displayed an elongated, bipolar phenotype, resembling immature astrocytes and glial progenitors whereas those from WT mice had a reactive, hypertrophied phenotype. Taken together, our data demonstrate that RGC-32 plays an important role in mediating TGF-β-induced reactive astrogliosis in EAE. Therefore, RGC-32 may represent a new target for therapeutic intervention in MS.     

C5b-9-activated, K(v)1.3 channels mediate oligodendrocyte cell cycle activation and dedifferentiation

Voltage-gated potassium (K_v) channels play an important role in the regulation of growth factor-induced cell proliferation. We have previously shown that cell cycle activation is induced in oligodendrocytes (OLGs) by complement C5b-9, but the role of K_v channels in these cells had not been investigated. Differentiated OLGs were found to express K_v1.4 channels, but little K_v1.3. Exposure of OLGs to C5b-9 modulated K_v1.3 functional channels and increased protein expression, whereas C5b6 had no effect. Pretreatment with the recombinant scorpion toxin rOsK-1, a highly selective K_v1.3 inhibitor, blocked the expression of K_v1.3 induced by C5b-9. rOsK-1 inhibited Akt phosphorylation and activation by C5b-9 but had no effect on ERK1 activation. These data strongly suggest a role for K_v1.3 in controlling the Akt activation induced by C5b-9. Since Akt plays a major role in C5b-9-induced cell cycle activation, we also investigated the effect of inhibiting K_v1.3 channels on DNA synthesis. rOsK-1 significantly inhibited the DNA synthesis induced by C5b-9 in OLG, indicating that K_v1.3 plays an important role in the C5b-9-induced cell cycle. In addition, C5b-9-mediated myelin basic protein and proteolipid protein mRNA decay was completely abrogated by inhibition of K_v1.3 expression. In the brains of multiple sclerosis patients, C5b-9 co-localized with NG2⁺ OLG progenitor cells that expressed K_v1.3 channels. Taken together, these data suggest that K_v1.3 channels play an important role in controlling C5b-9-induced cell cycle activation and OLG dedifferentiation, both in vitro and in vivo.     

Risk management in radiology departments

Medical imaging and interventional radiology sustained prompt changes in the last few years, mainly as a result of technology breakthroughs, rise in workload, deficit in workforce and globalization. Risk is considered to be the chance or possibility of incurring loss or of a negative event happening that may cause injury to patients or medical practitioners. There are various causes of risks leading to harm and injury in radiology departments, and it is one of the objectives of this paper to scrutinize some of the causes. This will drive to consideration of some of the approaches that are used in managing risks in radiology. This paper aims at investigating risk management in radiology, and this will be achieved through a thorough assessment of the risk control measures that are used in the radiology department. It has been observed that the major focus of risk management in such medical setting is to reduce and eliminate harm and injury to patients through integration of various medical precautions. The field of Radiology is rapidly evolving due to technology advances and the globalization of healthcare. This ongoing development will have a great impact on the level of quality of care and service delivery. Thus, risk management in radiology is essential in protecting the patients, radiologists, and the medical organization in terms of capital and widening of the reputation of the medical organization with the patients.