Sequential use of ferumoxide particles and gadolinium chelate for the evaluation of focal liver lesions on MRI

This study describes the sequential use of ferumoxide (superparamagnetic iron oxide) particles and nonspecific extracellular gadolinium chelate (Gd) for evaluation of focal liver lesions on MRI to evaluate order of contrast administration and imaging effect of the first contrast agent on sequences acquired after the second contrast agent. Thirteen patients underwent MR examinations that included ferumoxide and Gd. The order and timing of administration were as follows: separate sessions (three patients; Gd study 4-19 days before ferumoxide study), same session, Gd first (seven patients; Gd study 1-2 hours before ferumoxide study), and same session, ferumoxide first (three patients; ferumoxide administered less than 1 hour before Gd study). Postcontrast sequences were reviewed in a randomized, blinded fashion by two separate investigators. Determination was made regarding whether (a) the presence of the first agent administered could be detected on sequences obtained after the second agent and (b) the presence of the first agent interfered with the image quality of those sequences. No evidence for the presence of Gd was appreciated by either observer on postferumoxide sequences acquired in separate session studies. In same session, Gd first studies, the presence of Gd was observed in six of seven patients on T1-weighted spoiled gradient-echo (SGE) images obtained after ferumoxide administration. The presence of Gd was not apparent in seven of seven patients on T2-weighted fat-suppressed images obtained after ferumoxide. In same session, ferumoxide first studies, the presence of ferumoxide was appreciated on post-Gd sequences in two of three patients. The presence of ferumoxide did not appreciably diminish image quality on those sequences. Exact agreement was achieved by the independent investigators. Our results suggest that Gd and ferumoxide can be administered sequentially within one study session without substantial loss of diagnostic information obtained on sequences performed after administration of the second contrast agent. Administrating Gd first resulted in less of an effect of the visualization of the first agent on sequences acquired after the second agent.     

Mechanisms of arrhythmias: enhanced automaticity and reentry

Table 2 provides an overview of the classifications of antiarrhythmic agents, their actions, and their uses against reentrant arrhythmias and those caused by enhanced automaticity. Table 3 reviews many of the differences between the two mechanisms of arrhythmias: enhanced automaticity and reentry. Clinical distinction will assist in the most appropriate choice of therapy for terminating cardiac arrhythmias.     

Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen‐induced immunity and prevents allergic pulmonary pathology in a murine model

Background Virulent Bordetella pertussis, the causative agent of whooping cough, exacerbates allergic airway inflammation in a murine model of ovalbumin (OVA) sensitization. A live genetically attenuated B. pertussis mucosal vaccine, BPZE1, has been developed that evokes full protection against virulent challenge in mice but the effect of this attenuated strain on the development of allergic responses is unknown. Objective To assess the influence of attenuated B. pertussis BPZE1 on OVA priming in a murine model of allergic airway inflammation. Methods Mice were challenged with virulent or attenuated strains of B. pertussis, and sensitized to allergen (OVA) at the peak of bacterial carriage. Subsequently, airway pathology, local inflammation and OVA‐specific immunity were examined. Results In contrast to virulent B. pertussis, live BPZE1 did not exacerbate but reduced the airway pathology associated with allergen sensitization. BPZE1 immunization before allergen sensitization did not have an adjuvant effect on allergen specific IgE but resulted in a statistically significant decrease in airway inflammation in tissue and bronchoalveolar lavage fluid. BPZE1 significantly reduced the levels of OVA‐driven IL‐4, IL‐5 and IL‐13 but induced a significant increase in IFN‐γ in response to OVA re‐stimulation. Conclusions These data demonstrate that, unlike virulent strains, the candidate attenuated B. pertussis vaccine BPZE1 does not exacerbate allergen‐driven airway pathology. BPZE1 may represent an attractive T‐helper type 1 promoting vaccine candidate for eradication of whooping cough that is unlikely to promote atopic disease.     

Anterior colporrhaphy: why surgeon performance is paramount

Anterior compartment repair is one of the most challenging issues in reconstructive pelvic surgery. Previous studies using strict anatomic criteria suggested a high failure rate after anterior colporrhaphy, prompting increased use of augmented repairs in the past decade. More recent studies suggest anterior colporrhaphy may provide symptom relief similar to that seen with augmented repairs without the risks associated with placement of mesh. There is a wide range of success rates for anterior colporrhaphy in the literature. The wide variation implies surgeon performance is a key issue in the success or failure of anterior compartment repair. It is critical to begin measuring and reporting surgeon performance in research trials and monitoring surgeon performance in clinical practice in order to make meaningful comparisons of surgical techniques and improve patient care.     

Chronic kidney disease: a new look at pathogenetic mechanisms and treatment options

The concept of renoprotection has evolved significantly, driven by improved understanding of the pathophysiology of chronic kidney disease (CKD) and the advent of novel treatment options. Glomerular hyperfiltration, hypertension and proteinuria represent key mediators of CKD progression. It is increasingly recognized that proteinuria may actually be pathological and etiological in CKD progression and not just symptomatic. It initiates a sequence of events involving activation of proinflammatory and profibrotic signaling pathways in proximal tubular epithelial cells with transmission of the disease to the tubulointerstitium and progression to end-stage kidney disease (ESKD). Although the etiology and epidemiology of pediatric CKD differs to that in adults, studies in the various animal models of kidney disease, from obstructive uropathy to glomerulonephritis, have revealed that many common proinflammatory and profibrotic pathways are induced in progressive proteinuric CKD, irrespective of the primary disease. This pathomechanistic overlap therefore translates into the potential for common treatment targets for a wide spectrum of kidney diseases. In this review we therefore discuss the experimental and clinical evidence for an array of prospective future drug treatments of CKD progression. While conceptually promising, clear definitive evidence beyond preclinical data does not exist for many of these treatments, and others are limited by serious adverse effects. More studies are needed before general recommendations can be given.     

A prospective randomised comparison of cefotaxime vs. netilmicin vs. cefotaxime plus netilmicin in the treatment of hospitalised patients with serious sepsis

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.