Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy

Neuronal accumulation of oligomeric amyloid-β (Αβ) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Aβ stress to neurons by immigration into the brain and phagocytosis of Αβ. We tested migration and export across a blood-brain barrier model, and phagocytosis and clearance of Αβ by AD and normal subjects’ macrophages. Both AD and normal macrophages were inhibited in Αβ export across the blood-brain barrier due to adherence of Aβ-engorged macrophages to the endothelial layer. In comparison to normal subjects’ macrophages, AD macrophages ingested and cleared less Αβ, and underwent apoptosis upon exposure to soluble, protofibrillar, or fibrillar Αβ. Confocal microscopy of stained AD brain sections revealed oligomeric Aβ in neurons and apoptotic macrophages, which surrounded and infiltrated congophilic microvessels, and fibrillar Aβ in plaques and microvessel walls. After incubation with AD brain sections, normal subjects’ monocytes intruded into neurons and uploaded oligomeric Aβ. In conclusion, in patients with AD, macrophages appear to shuttle Aβ from neurons to vessels where their apoptosis may release fibrillar Aβ, contributing to cerebral amyloid angiopathy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. J. Zaghi and B. Goldenson contributed equally.     

Evolution of endoscopic management of ectopic ureterocele: a new approach

PURPOSE: We report the evolution of endoscopic treatment of ectopic ureteroceles from the unroofing technique to a novel approach using concomitant ureterocele double puncture and intraureterocele fulguration. We also compare the results of different endoscopic modalities at a single center. MATERIALS AND METHODS: We reviewed the records of 46 children with ectopic ureteroceles who were treated endoscopically between 1995 and 2005. The patients were divided into 2 main groups. Group 1 included 17 patients who underwent common endoscopic treatments, including ureterocele incision (4 patients), single ureterocele puncture (4), and single puncture with insertion of a Double-J stent (9). Group 2 included 29 children who underwent ureterocele double puncture and fulguration of the anterior and posterior walls of the collapsed ureterocele after insertion of a Double-J stent into both punctured sites. We also managed concomitant vesicoureteral reflux by endoscopic injection of tricalcium phosphate ceramic into the subureteral region. RESULTS: Total success rates in group 1 were 0%, 25% and 33% in patients who underwent ureterocele incision, single ureterocele puncture and single puncture with insertion of a stent, respectively. Total success rate in group 2 was 90% (p<0.05). New onset vesicoureteral reflux developed in 8 patients (47%) in group 1, of which 6 were in ureterocele moieties, and in 8 patients (28%) in group 2, with none in a ureterocele moiety (p<0.01). A total of 13 patients (76%) in group 1 required open surgical intervention, compared to 3 (10%) in group 2 (p<0.05). CONCLUSIONS: This new endoscopic approach is highly effective in the treatment of children with ectopic ureteroceles.     

Infantile bladder rupture during voiding cystourethrography

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.     

HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples suspicious for mycobacterial infections

Various molecular methods have been used for the rapid identification of mycobacterial species. In this survey, evaluation of antibiotic resistance and PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was carried out for identification of non-tuberculosis mycobacteria (NTM) isolates from different clinical specimens. Forty-eight different mycobacterial isolates were selected and followed by the conventional and PRA of hsp65 for species identification. The antibiotic susceptibility test was carried out according to standard methods. A 439 bp PCR product of hsp65 in all selected isolates was amplified and digested with the BstEII and HaeIII restriction enzymes. The restriction fragment length polymorphism (RFLP) patterns were analyzed for species identification. Using PRA for 48 mycobacterial selected isolates, including 15 M. tuberculosis, one M. bovis and all 32 isolates of NTM, revealed 11 different species among the NTM isolates. The most frequent NTM isolates were M. kansasii, M. gordonae III, M. marinum, M. chelonae, M. scrofluaceum and M. gastri. In most cases, the PRA results were perfectly in accordance with the classical biochemical method. Combination of resistance to rifampin and isoniazid was present among M. kansasi, M. gordoniae III, M. scrofluaceum, M. chelonae, M. marinum, M. gastri, M. gordoniae II and M. trivale isolates. A high incidence of co-resistance to six, five, four and three anti-TB drugs was observed in 18.5%, 9.1%, 6.6% and 11.7% of all NTM isolates, respectively. Our results showed that PRA, in comparison with classical methods, is rapid and accurate enough for the identification of mycobacterial species from LJ medium. Additionally, we found that in Iran we have a highly diverse population of NTM isolates among patients suspected of having TB.     

Analysis of baseline parameters in the HALT polycystic kidney disease trials

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60 ml/min per 1.73 m(2). Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25-60 ml/min per 1.73 m(2). We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log-transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log-transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity.