Results of the pilot treatment of 9 patients with chronic lymphocytic leukemia or CLL lymphoplasmacytoid lymphoma by the CHOP protocol

In a group of 9 patients with chronic lymphocytic or lymphoplasmocytic leukaemia in clinical stage from 2 to 4 (classification of Rai et al.) 8 various CHOP programmes (cyclophosphamide, hydroxyldaunomycin, oncovin, prednisone) were used. In 6 cases (67%) partial remission was obtained, with normalization of peripheral blood and bone marrow patterns, with statistically significant decrease of the proportion of cells forming rosettes with murine erythrocytes, and with reduction or full normalization of the size of previously enlarged lymph nodes. In one case the control examination of a lymph node failed to demonstrate the previously present clone of cells with chromosomal aberration, although in histological examination the diagnosis of lymphoplasmocytic lymphoma was maintained. In the remaining 3 cases no partial remission was noted, and in one case progression was recognized. We think similarly as the French haematologists studying chronic lymphatic leukaemia, that the CHOP programme is effective in the treatment of chronic lymphatic or lymphoplasmocytic leukaemia.     

Late potentials: are they related to cardiovascular complications in children with type 1 diabetes?

INTRODUCTION: The aim of our study was to assess the influence of cardiovascular complications on the occurrence of late ventricular potentials (LP) in children with diabetes mellitus type 1. MATERIALS AND METHODS: 72 children (36 boys and 36 girls), with average course of diabetes type 1 of 6.5+/-2.8 years, were included into the study. Standard physical examination, blood pressure measurements, signal-averaged electrocardiogram (SAECG), autonomic test, 24-h Holter monitoring, and Doppler echo investigations were performed. The control group consisted of 55 sex- and age-matched healthy children. We utilised nonlinear logistic regression analysis to assess the effect of disease duration, albuminuria, insulin demand, cardiac autonomic neuropathy (CAN), heart rate variability (HRV) indices, diabetes complication score, metabolic control, systolic and diastolic blood pressure, left ventricular parameters, and ventricular arrhythmias on LP occurrence. RESULTS: LP was discovered in 12 patients with diabetes and in 1 from the control group (P<.014). Diabetic children with LPs had thicker left ventricular posterior wall (LVPW) and longer diabetes duration time than children without LP (P<.045 and.031, respectively). Nonlinear regression model shows that duration of diabetes, CAN, and LVPW were the strongest independent parameters of LP occurrence (P<.001,.01 and.005, respectively). CONCLUSIONS: Diabetes type 1 is associated not only with increased occurrence of abnormal SAECG but also with LP presence. The disease duration, posterior wall thickness, and CAN are independent predictors of LP appearance in diabetes type 1 children. The presence of cardiovascular complication has no influence on LP occurrence in diabetic children.     

IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo

A variety of complement components have been detected on apoptotic cells and proposed to facilitate recognition and/or ingestion by phagocytes. The triggers for complement activation remain uncertain. To determine the role of IgM in classical pathway activation and clearance of apoptotic cells in vitro and in vivo, we quantified these parameters in mice deficient in serum IgM (sIgM). Phagocytosis by bone marrow-derived macrophages of apoptotic cells incubated with serum deficient in sIgM was markedly reduced, similar to apoptotic cells incubated with C1q deficient serum in vitro. Similarly, intraperitoneal clearance of apoptotic cells and cellular C3 deposition were significantly reduced in mice deficient in sIgM compared to wild-type mice. Clearance and C3 deposition were reconstituted by addback of IgM. In mice deficient in both sIgM and C1q, addback of both serum factors was required for restoration of clearance. These findings indicate that, on a quantitative basis, sIgM is a potent factor required for intraperitoneal phagocytosis of apoptotic cells, and further demonstrate that IgM and C1q work in concert to activate complement, resulting in C3 deposition on the apoptotic cell surface and ultimately, efficient clearance of the apoptotic cell by macrophages.     

β‐amyloid and ATP‐induced diffusional trapping of astrocyte and neuronal metabotropic glutamate type‐5 receptors

β‐Amyloid (Aβ) oligomers initiate synaptotoxicity following their interaction with the plasma membrane. Several proteins including metabotropic glutamate type 5 receptors (mGluR5s) contribute to this process. We observed an overexpression of mGluR5s in reactive astrocytes surrounding Aβ plaques in brain sections from an Alzheimer's disease mouse model. In a simplified cell culture system, using immunocytochemistry and single molecule imaging, we demonstrated a rapid binding of Aβ oligomers on the plasma membrane of astrocytes. The resulting aggregates of Aβ oligomers led to the diffusional trapping and clustering of mGluR5s. Further, Aβ oligomers induced an increase in ATP release following activation of astroglial mGluR5s by its agonist. ATP slowed mGluR5s diffusion in astrocytes as well as in neurons co‐cultured with astrocytes. This effect, which is purinergic receptor‐dependent, was not observed in pure neuronal cultures. Thus, Aβ oligomer‐ and mGluR5‐dependent ATP release by astrocytes may contribute to the overall deleterious effect of mGluR5s in Alzheimer's disease. GLIA 2013;61:1673–1686     

„Supporting Siblings“

Background

The special life situation of siblings of children with chronic health conditions (CHCs) and/or disabilities can be a risk factor for adjustment problems. Therefore, healthy siblings are in need of increased attention in primary prevention. The present article describes the pilot study of the primary prevention life skills training called “Supporting Siblings” which has been developed for the target group of siblings of children with CHCs and/or disabilities.

Objectives

The main aims of the pilot study were to examine the acceptance and feasibility of the training as well as the first effects on coping and health-related quality of life (HRQoL).

Methods

The study was based on a pre-post follow-up waiting list control group design. The intervention group as well as the waiting list control group consisted of six siblings of children with CHCs and/or disabilities aged between 7 and 12 years (mean age M?=?9.6 years, SD?±?1.5 years). A coping questionnaire for children and adolescents (SVF-KJ) and the KIDSCREEN-27 were used to review the evaluation criteria.

Results

Considering the acceptance of the training, a high rate of satisfaction became apparent for the participants. Moreover, indications of beneficial changes in terms of the evaluation criteria emerged. The coping pattern and the HRQoL improved in a clinically relevant way. The initial positive results of the intervention were confirmed by parent proxy reports.

Conclusion

The life-skills training “Supporting Siblings” is a very promising and well-accepted approach to primary prevention for siblings of children with CHCs and/or disabilities. The results have to be confirmed by a larger representative sample.     

Trans-sternal approach to the cervicothoracic junction

Cervicothoracic junction and upper thoracic spine down to T4 can be reached through anterior approach via sternotomy. Transsternal approach is the best route to gain access to lesions localized within vertebral bodies of the upper thoracic spine allowing for their resection, interbody fusion and replacement with bone cement. Consecutive modifications of transsternal approach evolved toward less extensive osteotomy from full median sternotomy, through manubriotomy with clavicle resection and partial lateral manubriotomy. Less extensive modifications provide limited lateral exposure of the spine and are more demanding technically. We present two cases of upper thoracic spine tumours operated on through full medial sternotomy. We believe that median sternotomy has several advantages over less extensive modifications: it is technically simple to perform for trained thoracic surgeon, safer as it provides better exposure of the mediastinum and thus sufficient control of great vessels including subclavian ones, gives better exposure of T3, T4 and even T5 vertebral bodies, allows perpendicular sight and attack to anterior surface of the upper thoracic spine and therefore good visualizing of the posterior longitudinal ligament and dura, do not destabilize shoulder girdle nor affect function of the upper limb. Additional caudal exposure of the thoracic spine as down as T5 can be obtained by dissecting a plane between the brachiocephalic vein, vena cava superior and ascending aorta.     

Tracker-assisted laser in situ keratomileusis for myopia using the autonomous scanning and tracking laser: 12-month results

OBJECTIVE: To determine the safety, efficacy, and predictability of the Autonomous scanning and tracking laser for the correction of myopia and myopic astigmatism with laser in situ keratomileusis (LASIK) procedure. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The first 129 consecutive eyes with up to -13.00 diopters (D) of myopia and -5.00 D of astigmatism. INTERVENTION: Myopic tracker-assisted LASIK (T-LASIK) using the Autonomous Laser (Alcon Summit Autonomous, Waltham, MA) and Hansatome microkeratome (Bausch & Lomb Surgical, Bracknell, England). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), manifest spherical equivalent (MSE), best spectacle-corrected visual acuity (BSCVA), and complications were studied. RESULTS: At 12 months, the mean MSE was -0.02 +/- 1.01 D, with 79.1% of eyes within 0.5 D and 89.9% of eyes within 1 D of the intended correction. UCVA was 20/20 or better in 71.4%, 20/25 or better in 78.5%, and 20/40 or better in 92.8% of eyes. Two eyes (1.6%) lost 2 lines and five eyes (3.8%) gained 2 lines of BSCVA. Sixteen eyes (12.4%) required retreatment to correct residual myopia or astigmatism. After retreatment, 14 of 16 eyes were within 0.5 D of emmetropia. Nine eyes (6.9%) had minor flap complications; two eyes (1.6%) had grade 2 diffuse lamellar keratitis, of which one eye had associated peripheral flap melt. One eye showed slight decentration; this eye was rolling throughout the procedure. All eyes had some dryness, with 10% severe enough to require temporary punctual occlusion with plugs. CONCLUSIONS: T-LASIK for myopic astigmatism with the Autonomous Laser is relatively safe, effective, and predictable. The tracker seems to be effective, and the complications are relatively few. Retreatment rates are acceptable and can be performed safely and effectively to improve visual outcome. The outcomes are comparable with other published data.     

A practical technique for differentiation of subepidermal bullous diseases: localization of in vivo-bound IgG by laser scanning confocal microscopy

OBJECTIVE: To develop a practical technique to distinguish autoimmune subepidermal bullous diseases. DESIGN: A prospective study. SETTING: Academic referral center-the Department of Dermatology, Medical University of Warsaw.Patients Forty-two patients fulfilling clinical, immunological, and/or immunoelectron microscopic criteria for bullous pemphigoid (n = 31), mucous membrane pemphigoid (n = 6), or epidermolysis bullosa acquisita (n = 5), diagnosed as having disease and treated from January 1, 1997, to December 31, 2002. MAIN OUTCOME MEASURES: We applied laser scanning confocal microscopy to determine the localization of in vivo-bound IgG at the basement membrane zone in biopsy specimens taken from patients' skin to compare the localization of basement membrane zone markers: antibody against beta4 integrin, antibody against laminin 5, and antibody against type IV collagen. In vivo-bound IgG was visualized by labeling with fluorescein isothiocyanate-conjugated anti-human IgG antibody, whereas basement membrane zone markers were labeled with anti-mouse Cy5-conjugated antibodies. RESULTS: In patients with bullous pemphigoid, in vivo-bound IgG was localized on the epidermal side of laminin 5 and co-localized with beta4 integrin. In patients with mucous membrane pemphigoid, IgG was in vivo bound to the dermal-epidermal junction between localization of laminin 5 and type IV collagen. In patients with epidermolysis bullosa acquisita, in vivo-bound IgG was present on the dermal side of type IV collagen. CONCLUSIONS: Laser scanning confocal microscopy allows precise localization of in vivo-bound IgG in patients' skin and, thus, it is a rapid method for the differentiation of mucous membrane pemphigoid from bullous pemphigoid and epidermolysis bullosa acquisita. This tool is suitable for the routine diagnosis of individual patients and for retrospective studies. This method is of special value in those patients in whom circulating autoantibodies are not detectable.     

Proinflammatory cytokines (IL-6, TNF-alpha) and cardiac troponin I (cTnI) in serum of young people with ventricular arrhythmias

In the most cases the origin of ventricular arrhythmias is ischaemic, necrosis focus or presence of the connective tissue in cardiac muscle. The aim of the study was to evaluate troponin I (cTnI), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) vs in young subject with ventricular arrhythmias. Into the study group included young people without organic heart diseases, dyselectrolitemia, with normal ECG which has not elevated levels of C-reactive protein (55 persons). The control group consisted of 22 healthy persons. The values of cTnI were not increased. The TNF-alpha concentrations were elevated in persons with ventricular arrhythmias (92 +/- 232 pg/mL vs. 2 +/- 1 pg/mL, p < 0.001). The IL-6 concentrations were slightly elevated without statistical significance (1.5 +/- 4.5 pg/mL i 0.1 +/- 0.04 pg/mL, p = 0.06). CONCLUSIONS: There was no evidence of myocardial injury in young people with ventricular arrhythmias (cTnI). We noted increase levels of proinflammatory cytokines. It might suggest that the background of ventricular arrhythmias is inflammation.