Proteomic analysis of mantle-cell lymphoma by protein microarray

Mantle-cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma (NHL) that behaves aggressively and remains incurable. In order to understand the pathogenesis of MCL and design new therapies, it is important to accurately analyze molecular changes in pathways dysregulated in MCL. We used antibody microarrays to compare patterns of protein expression between CD19(+) purified B lymphocytes from normal tonsil and 7 cases of histologically confirmed MCL. Protein overexpression was defined as a higher than 1.3-fold or 2-fold increase in at least 67% of tumor samples compared with normal B-cell control. Of the polypeptides, 77 were overexpressed using the higher than 1.3-fold cutoff, and 13 were overexpressed using the 2-fold cutoff. These included cell cycle regulators (regulator of chromosome condensation 1 [RCC1], murine double minute 2 [MDM2]), a kinase (citron Rho-interacting kinase [CRIK]), chaperone proteins (heat shock 90-kDa protein [Hsp90], Hsp10), and phosphatase regulators (A-kinase anchor protein 1 [AKAP149], protein phosphatase 5 [PP5], and inhibitor 2). The elevated expression of some of these polypeptides was confirmed by immunoblotting and immunohistochemistry, whereas elevated expression of others could not be confirmed, illustrating the importance of confirmatory studies. This study describes a novel technique that identifies proteins dysregulated in MCL.     

Unusual disposition of lateral circumflex femoral artery: Anatomical description and clinical implications

The anatomical knowledge of arterial variations of lower limb is of utmost significance for the present day surgeons and interventional radiologists for minimizing complications during vascular reconstructive procedures, catheterization procedures and surgical intervention for embolism. Lateral Circumflex Femoral Artery(LCFA) isan important branch of Profunda Femoris artery and precise knowledge of its variations can be of great relevance during surgical and radiological procedures in femoral region. The present study reports a unique case of anomalous route taken by LCFA posterior to femoral nerve associated with a prominent muscular branch from Femoral artery mimicking the course of LCFA. Documentation of such variations is highly significant. It may serve as guideline for surgeons in reducing the incidence of postoperative complications where LCFA is used as a long vascular pedicle in anterolateral perforator thigh flap and in breast reconstruction after mastectomy. Ignorance of such variations can lead to fatal intraoperative haemorrhage and incapacitating sensory and motor deficit due to injury to femoral nerve branches which are closely related to these vessels.     

A Novel Segment Classification for Multifocal and Multicentric Breast Cancer to Facilitate Breast‐Conservation Treatment

Breast conservation treatment (BCT) is an appropriate alternative to mastectomy for the treatment of unifocal breast cancer. Multifocal and multicentric breast cancers (MFMCBC) challenge conventional indications for BCT and are often treated with mastectomy. Following progress in treatment strategies for unifocal tumors, there was a movement to evaluate the use of BCT for MFMCBC. Now a growing body of evidence from retrospective data has emerged, demonstrating acceptable local control and overall survival rates with BCT for MFMCBC. Prospective studies are needed to confirm these findings. One of the possible barriers to such trials is the absence of a standardized classification and nomenclature for MFMCBC at this point in time. A novel segment classification is presented in this article in an endeavor to overcome this deficiency and allow future work on this issue.     

The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy: A 15-year follow-up of 32,476 total knee arthroplasties in the Norwegian Arthroplasty Register

Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material.Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis.Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8).Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty.High tibial osteotomy (HTO) is a well-established joint preserving procedure for the treatment of medial knee osteoarthritis. The goal is to achieve unloading of the affected medial compartment of the knee to prevent or postpone the need for an artificial knee joint. This is performed by slightly overcorrecting the knee joint from varus malalignment to valgus or neutral position. Osteotomy was a standard treatment option for unicompartmental knee osteoarthritis in earlier years before knee arthroplasty was a surgical option, but osteotomy lost importance in the 1980s because of the success of knee replacement surgery (Smith et al. 2013). However, there has been an increase in osteotomies during the last 15 years, especially in younger patients in some countries (Seil et al. 2013). National arthroplasty registers have demonstrated higher risk of revision for knee arthroplasty in younger patients (under the age of 60) (NAR 2014, SKAR 2013). The 2 most commonly used methods for HTO are lateral closing wedge and medial opening wedge osteotomy. Both methods have shown improvement in knee pain and function (Naudie et al. 1999, van Raaij et al. 2008, Efe et al. 2011, W-Dahl et al. 2012). Nevertheless, some patients later require a second procedure, a total knee arthroplasty (Naudie et al. 1999), depending on the degree of osteoarthritis, their level of pain and function, and the degree of correction achieved. Although total knee arthroplasty appears to be technically more challenging after HTO in cases with severe overcorrection, bone stock loss, altered joint line (Figures 1 and ​and2),2), or patella infera, only a few studies have found inferior results compared to primary TKA (Windsor et al. 1988, Parvizi et al. 2004, Haslam et al. 2007, Farfalli et al. 2012). The aim of this study was to evaluate the risk of revision after TKA, comparing primary TKA with and without previous high tibial osteotomy using data from the Norwegian Arthroplasty Register (NAR).Open in a separate windowFigure 1.Example of extra-articular malalignment after high tibial osteotomy (HTO) with opening wedge technique. The red line on the left radiograph (a) indicates the mechanical axis lateral to the knee joint. The radiograph to the right (b) indicates the extra-articular angulation of the tibia in the osteotomy area.Open in a separate windowFigure 2.Example of intra-articular malalignment after high tibial osteotomy (WTO) with closing wedge technique. The solid red line indicates that the tibial plateau has been elevated medially and is not perpendicular to the tibial axis.     

Protective Effects of Estradiol on Myocardial Contractile Function Following Hemorrhagic Shock and Resuscitation in Rats

Background:

Hemorrhagic shock (HS) results in myocardial contractile dysfunction. Studies showed that 17β-estradiol protects the myocardium against contractile dysfunction. The study investigated the cardioprotective effects of treatment with 17β-estradiol before resuscitation following 1 h of HS and resuscitation.

Methods:

Male Sprague-Dawley rats were assigned to 2 sets of experimental protocols: Ex vivo and in vivo treatment and resuscitation. Each set had three experimental groups (n = 6 per group): Normotensive (N), HS and resuscitation (HS-R) and HS rats treated with 17β-estradiol (E) and resuscitated (HS-E-R). Rats were hemorrhaged over 60-min to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff system. In the 17β-estradiol treated group, 17β-estradiol 280 µg/kg was added for the first 5 min. Cardiac function was measured. Left ventricular generated pressure (LVGP) and +dP/dt were calculated. In the in vivo group, rats were treated with 17β-estradiol 280 µg/kg s.c. after 60-min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30-min to restore normotension.

Results:

Treatment with 17β-estradiol before resuscitation in ex vivo treated and resuscitated isolated hearts and in the in vivo treated and resuscitated rats following HS improved myocardial contractile function. In the in vivo treated group, LVGP and +dP/dt max were significantly higher in 17β-estradiol treated rats compared to the untreated group (LVGP 136.40 ± 6.61 compared to 47.58 ± 17.55, and +dP/dt 661.85 ± 49.88 compared to 88.18 ± 0.85). Treatment with 17β-estradiol improved LVGP following HS.

Conclusions:

The results indicate that treatment with 17β-estradiol before resuscitation following HS protects the myocardium against dysfunction.     

Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma

Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting beta2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4-80 years (FEV1 60-100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud + SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45-47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.     

Vascular cell adhesion molecule-1 (VCAM-1), flow mediated dilatation (FMD) and carotid intima media thickness (IMT) in children with juvenile idiopathic arthritis: Relation to disease activity,functional status and fatigue

Background

There is risk of premature atherosclerosis in juvenile idiopathic arthritis (JIA) patients which predisposes to cardiovascular disease (CVD) in adulthood. This can be assessed by flow mediated dilatation (FMD) and carotid intima media thickness (IMT) of the arterial wall and by soluble vascular cell adhesion molecule (sVCAM-1).