The anatomy of the cardiac veins in mice

Although the cardiac coronary system in mice has been the studied in detail by many research laboratories, knowledge of the cardiac veins remains poor. This is because of the difficulty in marking the venous system with a technique that would allow visualization of these large vessels with thin walls. Here we present the visualization of the coronary venous system by perfusion of latex dye through the right caudal vein. Latex injected intravenously does not penetrate into the capillary system. Murine cardiac veins consist of several principal branches (with large diameters), the distal parts of which are located in the subepicardium. We have described the major branches of the left atrial veins, the vein of the left ventricle, the caudal veins, the vein of the right ventricle and the conal veins forming the conal venous circle or the prepulmonary conal venous arch running around the conus of the right ventricle. The venous system of the heart drains the blood to the coronary sinus (the left cranial caval vein) to the right atrium or to the right cranial caval vein. Systemic veins such as the left cranial caval, the right cranial caval and the caudal vein open to the right atrium. Knowledge of cardiac vein location may help to elucidate abnormal vein patterns in certain genetic malformations.     

An example of a bootstrap technique application for judging a variability of method performance estimates and its consequences for quality control planning

BACKGROUND: Flexible fitting of quality control procedures to method performance is an inseparable element of a cost-effective quality management strategy. However, opinions on method performance, based on a restricted number of quality control results used to calculate bias and imprecision, can vary due to the random nature of the data-gathering process. METHODS: We present an example of the bootstrap technique application in evaluating method performance estimates. RESULTS: Our analysis reveals substantial variability in method performance assessment results that should not be omitted. We suggest that the best way of using information concerning method performance is to consider the information in a probabilistic manner. Method performance is a feature presented with an element of probability. The effectiveness of a quality control procedure should be assessed with regard to this probability. CONCLUSIONS: Presented example of a bootstrap technique application increases our awareness of the uncertainty that accompanies method performance judgment and quality control planning.     

Toxicity of pamam‐coated gold nanoparticles in different unicellular models

Polyamidoamine (PAMAM) dendrimers are used for many pharmaceutical and biomedical applications. However, the toxicological risks of several PAMAM‐based compounds are still not fully evaluated, despite evidences of PAMAM deleterious effects on biological membranes, leading to toxicity. In this report, we investigated the toxicity of generation 0 PAMAM‐coated gold nanoparticles (AuG0 NPs) in four different models to determine how different cellular systems are affected by PAMAM‐coated NPs. Toxicity was evaluated in two mammalian cell lines, Neuro 2A and Vero, in the green alga Chlamydomonas reinhardtii and the bacteria Vibrio fischeri. AuG0 NP treatments reduced cell metabolic activity in algal and bacterial cells, measured by esterase enzymatic activity (C. reinhardtii) and luminescence emission (V. fischeri). EC50 value after 30 min of treatment was similar in both organisms, with 0.114 and 0.167 mg mL^?1 for C. reinhardtii and V. fischeri, respectively. On the other hand, AuG0 NPs induced no change of mitochondrial activity in mammalian cells after 24 h of treatment to up to 0.4 mg mL^?1 AuG0 NPs. Change in the absorption spectra of AuG0 NP in the mammalian cell culture media may indicate an alteration of NP properties that contributed to the low toxicity of AuG0 NPs in mammalian cells. For a safe development of PAMAM‐based nanomaterials, the difference of sensitivity between mammalian and microbial cells, as well as the modulation of NPs toxicity by medium properties, should be taken into account when designing PAMAM NPs for applications that may lead to their introduction in the environment. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 328–336, 2014.     

Rituximab in Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome

The outcome of steroid-dependent or frequently relapsing nephrotic syndrome of minimal change disease (MCD), mesangial proliferative GN (MesGN), or FSGS may be poor and with major treatment toxicity. This academic, multicenter, off-on trial (ClinicalTrials.gov #{"type":"clinical-trial","attrs":{"text":"NCT00981838","term_id":"NCT00981838"}}NCT00981838) primarily evaluated the effects of rituximab therapy followed by immunosuppression withdrawal on disease recurrence in 10 children and 20 adults with MCD/MesGN (n=22) or FSGS who had suffered ≥2 recurrences over the previous year and were in steroid-induced remission for ≥1 month. Participants received one dose (n=28) or two doses of rituximab (375 mg/m² intravenously). At 1 year, all patients were in remission: 18 were treatment-free and 15 never relapsed. Compared with the year before rituximab treatment, total relapses decreased from 88 to 22 and the per-patient median number of relapses decreased from 2.5 (interquartile range [IQR], 2–4) to 0.5 (IQR, 0–1; P<0.001) during 1 year of follow-up. Reduction was significant across subgroups (children, adults, MCD/MesGN, and FSGS; P<0.01). After rituximab, the per-patient steroid maintenance median dose decreased from 0.27 mg/kg (IQR, 0.19–0.60) to 0 mg/kg (IQR, 0–0.23) (P<0.001), and the median cumulative dose to achieve relapse remission decreased from 19.5 mg/kg (IQR, 13.0–29.2) to 0.5 mg/kg (IQR, 0–9.4) (P<0.001). Furthermore, the mean estimated GFR increased from 111.3±25.7 to 121.8±29.2 ml/min per 1.73 m² (P=0.01), with the largest increases in children and in FSGS subgroups. The mean height z score slope stabilized in children (P<0.01). Treatment was well tolerated. Rituximab effectively and safely prevented recurrences and reduced the need for immunosuppression in steroid-dependent or frequently relapsing nephrotic syndrome, and halted disease-associated growth deficit in children.Idiopathic nephrotic syndrome (NS) in children and young adults is almost invariably the clinical counterpart of a continuum of glomerular diseases ranging from the relatively frequent minimal change disease (MCD) and the less frequent mesangial proliferative GN (MesGN), which are predominantly observed in children, to the relatively uncommon FSGS that is observed more frequently in adult patients.¹ In a small minority of patients that are generally resistant to immunosuppressive therapies, the disease is due to molecular defects of one of the podocyte genes.² In all of the other cases, it appears to be immune-mediated, but the pathophysiologic process underlying glomerular injury remains poorly understood.³Independent of the underlying renal pathology, prednisone continues to be the cornerstone treatment at disease onset, achieving remission within 4 weeks in approximately 90% of children with MCD and in 20%–60% of those with FSGS.^4,5 However, 60%–70% of patients relapse after steroid tapering or withdrawal, and most require repeat courses of prednisone to achieve remission of recurrent episodes and/or the addition of other immunosuppressive medications, such as calcineurin inhibitors, mycophenolate mofetil, or alkylating agents, to reduce the number of relapses and prevent major side effects of steroid treatment.⁶ According to their relapse rate, these patients are classically labeled as “steroid-dependent” or “frequently relapsing”. In these patients, serious adverse effects of treatment associate with complications of relapsing episodes of heavy proteinuria. These are the patients in most urgent need of more effective and safer treatment.The possibility of a specific and, hopefully, safer approach to patients with steroid-dependent or frequently relapsing NS emerged in 2004 when the B cell–depleting mAb rituximab was reported to induce remission of proteinuria in a child with frequently relapsing NS secondary to MCD who had received this medication to cure a supervened idiopathic thrombocytopenic purpura.⁷ Subsequent uncontrolled observations found some effect of rituximab in patients with steroid-dependent or frequently relapsing MCD,^8–11 suggesting that B-cell immunity could play a key role in the pathophysiology of the disease. Controlled studies in support of this hypothesis, however, have been both scanty and almost confined to children^12,13 or to patients with MCD who were evaluated in the context of a retrospective, observational design.¹⁴ Indeed, less attention was given to adults and patients with FSGS given difficulties in designing adequately powered trials.Here, we designed a longitudinal, off-on study (ClinicalTrials.gov #{"type":"clinical-trial","attrs":{"text":"NCT00981838","term_id":"NCT00981838"}}NCT00981838) to evaluate the efficacy of rituximab in reducing the incidence of relapses and need for steroid and other immunosuppressive medications in children and adults with steroid-dependent or frequently relapsing NS due to MCD, MesGN, or FSGS. To minimize the side effects and costs of rituximab, we abandoned the standard four-dose protocol originally implemented for the treatment of B-cell lymphomas,¹⁵ and adopted a new B cell–driven regimen we found to achieve remission of NS in patients with idiopathic membranous nephropathy (IMN) as effectively as the standard protocol, but with fewer side effects and less costs.¹⁶     

Results of a comparative study analyzing octogenarians with renal cell carcinoma in a competing risk analysis with patients in the seventh decade of life

ObjectivesTo analyze clinicopathological features and survival of surgically treated patients with renal cell carcinoma (RCC)≥80 years of age in comparison with patients between the ages of 60 and 70 years.Materials and methodsThe data for 2,516 patients with a median follow-up of 57 months were retrieved from a multinational database (Collaborative Research on Renal Neoplasms Association [CORONA]), including data for 6,234 consecutive patients with RCC after radical or partial nephrectomy. Comparative analysis of clinicopathological features of 241 octogenarians (3.9% of the database) and 2,275 reference patients between the ages of 60 and 70 years (36.5%) was performed. Multivariable regression analysis adjusted for competing risks was applied to identify the effect of advanced age on cancer-specific mortality (CSM) and other-cause mortality (OCM). Furthermore, instrumental variable analysis was employed to reduce residual confounding by unmeasured parameters.ResultsSignificantly more women were present (50% vs. 40%, P = 0.004), and significantly less often nephron-sparing surgery was performed in octogenarians compared with the reference group (11% vs. 20%, P<0.001). Although median tumor size and stages did not significantly defer, older patients less often had advanced or metastatic disease (N+/M1) (4.6% vs. 9.6%, P = 0.009). On multivariable analysis, higher CSM (hazard ratio = 1.48, P = 0.042) and OCM rates (hazard ratio = 4.32, P<0.001) were detectable in octogenarians (c-indices = 0.85 and 0.72, respectively). Integration of the variable age group in multivariable models significantly increased the predictive accuracy regarding OCM (6%, P<0.001), but not for CSM. Limitations are based on the retrospective study design.ConclusionsOctogenarian patients with RCC significantly differ in clinical features and display significantly higher CSM and OCM rates in comparison with their younger counterparts.     

Analysis of Reoperations After Laparoscopic Adjustable Gastric Banding

Background and Objectives:

Laparoscopic adjustable gastric banding is considered the least invasive surgical option for the treatment of morbid obesity. Its initial popularity has been marred by recent long-term studies showing high complication rates. We sought to examine our experience with gastric banding and factors leading to reoperation.

Methods:

We reviewed retrospective data of 305 patients who underwent laparoscopic adjustable gastric banding between 2004 and 2011 at a single institution, 42 patients of whom required a reoperation, constituting 13.8%. Patients undergoing elective reoperations for port protrusion from weight loss as a purely cosmetic issue were excluded (n = 10). Patients'' demographic data, weight loss, time to reoperation, and complications were analyzed.

Results:

Of 305 patients, 42 (13.8%) required reoperations: 26 underwent band removal (8.5%) and 16 underwent port revision (5.2%). The mean weight and body mass index for all patients who underwent reoperations were 122.6 kg and 45.0 kg/m², respectively. The most common complication leading to band removal was gastric prolapse (n = 14, 4.6%). The most common indication for port revision was a nonfunctioning port (n = 10, 3.3%).

Conclusion:

Laparoscopic adjustable gastric banding was initially popularized as a minimally invasive gastric-restrictive procedure with low morbidity. Our study showed a 13.8% reoperation rate at 3 years'' follow-up. Most early reoperations (<2 years) were performed for port revision, whereas later reoperations (>2 years) were likely to be performed for band removal. Laparoscopic adjustable gastric banding is associated with high reoperation rates; therefore bariatric surgeons should carefully consider other surgical weight-loss options tailored to the needs of the individual patient that may have lower complication and reoperation rates.