Search

Amyloid aggregates of the protein α-synuclein (αS) called Lewy Bodies (LB) and Lewy Neurites (LN) are the pathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. We have previously shown that high extracellular αS concentrations can be toxic to cells and that neurons take up αS. Here we aimed to get more insight into the toxicity mechanism associated with high extracellular αS concentrations (50–100 μM). High extracellular αS concentrations resulted in a reduction of the firing rate of the neuronal network by disrupting synaptic transmission, while the neuronal ability to fire action potentials was still intact. Furthermore, many cells developed αS deposits larger than 500 nm within five days, but otherwise appeared healthy. Synaptic dysfunction clearly occurred before the establishment of large intracellular deposits and neuronal death, suggesting that an excessive extracellular αS concentration caused synaptic failure and which later possibly contributed to neuronal death. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: To evaluate the diagnostic efficacy of the office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) in the assessment of hypertension (HTN) in children with diabetes mellitus type 1 (T1DM). Methods: We analyzed OBP and ABPM measurements in 84 diabetic children (43 boys) obtained at a median age of 14.9 yr and 6.3 ± 3.5 yr after diagnosis of T1DM. OBP and ABPM results were converted into standard deviation scores (SDS). In addition, we analyzed blood pressure loads and nighttime dipping. The comparison between OBP and ABPM was performed using kappa coefficient and receiver operator curve (ROC). Results: HTN was diagnosed in 43/84 (51%) patients using OBP (>95th percentile), and in 24/84 (29%) patients using ABPM ( >=95th percentile during 24 h, day or night). Both methods were in agreement in 33 ABPM normotensive and 16 ABPM hypertensive patients (most had nighttime HTN); 32% patients had white-coat HTN and 9.5% patients had masked HTN. The kappa coefficient was 0.175 (95% CI from -0.034 to 0.384) suggesting poor agreement between OBP and ABPM. Diastolic OBP was a better predictor of ABPM HTN (ROC area under the curve (AUC) = 0.71 ± 0.06) than systolic OBP (AUC = 0.58 ± 0.07). The percentage of non-dippers ranged from 7 to 23% in ABPM normotensive patients, and 21-42% in ABPM hypertensive patients who also had significantly higher BP loads (p < 0.0001). Conclusion: Children with T1DM often suffer from nocturnal, white coat- and masked HTN, which can not be assessed and predicted by the OBP. [ABSTRACT FROM AUTHOR]

Gupta M, Diaz-Mitoma F, Feber J, Shaw L, Forget C, Filler G. Tissue HHV6 and 7 determination in pediatric solid organ recipients – a pilot study. Pediatr Transplantation 2003: 7: 458–463. © 2003 Blackwell Munksgaard Herpes virus infections remain a major challenge in solid organ transplantation. HHV6 and 7 blood viral load was associated with pathology after renal transplantation. Little is known about the significance of tissue HHV6 and 7 infections. A total of 18 tissue biopsies (13 kidney, three GI and two BAL) from nine pediatric transplant patients (five kidney, two liver, one combined liver and kidney and one bone marrow transplant) were subjected to blood HHV6 IgG and IgM testing. In addition, tissue HHV6 and 7 semi-quantitative PCR analysis with subsequent detection by ELISA and quantitative methods were applied to the same samples. We also studied four native kidney biopsies of children with other kidney disease. The results of the biopsies were correlated with clinical data. Of the transplant patients, 78% were HHV6 IgG positive. Six of nine had a positive IgM on at least one occasion, however, only two of nine transplant patients were symptomatic with a mixed CMV/EBV septic picture of multi-organ failure. Only these two patients had a significant tissue viral load for HHV6. Additionally, a very significant tissue viral load for HHV6 was detected in an immunocompromised patient 3 wk after a roseola-like febrile illness. The HHV6 copies were 31, 88 and 206 per 10 μL of DNA, respectively. In the patient who also had the fourth positive ELISA for HHV6 PCR product, the Multiplex PCR and restriction enzyme assay on its PCR product revealed a significant contribution by HHV7, while the HHV6-B signal was rather weak. Significant tissue HHV6 loads can be found in tissue biopsies from organ recipients with significant illness and also in native kidneys after primary infection. This may explain the high prevalence of HHV6 in transplanted kidneys. Further studies on HHV6 and 7 using molecular techniques should be supported. [ABSTRACT FROM AUTHOR]

Acute renal failure (ARF) is a rare but potentially fatal complication of diabetic ketoacidosis (DKA). Early recognition and aggressive treatment of ARF during DKA may im-prove the prognosis of these patients. We present a case report of a 12 year old female admitted to the hospital with severe DKA as the 1s t manifestation of her diabetes mellitus. She presented with severe metabolic acidosis, hypophosphatemia, and oliguric ARF. In addition, rhabdomyolysis was noted during the course of DKA which probably contributed to the ARF. Management of DKA and renal replacement therapy resulted in quick recovery of renal function. We suggest that early initiation of renal replacement therapy for patients with DKA developing ARF may improve the potentially poor outcome of patients with ARF associated with DKA.

Objective Input deprived (sub)networks of cortical neurons may become hyper excitable, possibly causing certain types of epilepsy. Electrical stimulation and application of the mildly excitatory neurotransmitter ghrelin have been shown to reduce this hyper excitability, suggesting that it is a generic feature of mild excitation. Therefore, we hypothesize that another mildly excitatory agent, orexin-A (OXA), should also reduce excitability. Methods We used cultures of cortical neurons on multi electrode arrays to measure network activity. If left in isolation, activity patterns typically contain bursts that reflect network hyper excitability. The relative contribution of bursts to the total amount of spikes was used as a measure for excitability and assessed by the burstiness index (BI = 1 → burst dominated; BI = 0 → no bursts). Results Acute application of 1 μM OXA significantly increased the level of activity from 1500 ± 650(SEM) to 3200 ± 1300 spikes/min. Burstiness index dropped from 0.75 ± 0.09 to 0.58 ± 0.09 indicating more dispersed firing. Conclusions Like electrical stimulation or ghrelin, OXA mildly activates cultured networks of cortical neurons and reduces burstiness. Key message Besides cellular hyper excitability, networks may also become hyper excitable in case of insufficient ongoing activation. This may be treated by mild activation, rather than the commonly used anti-epileptic drugs that aim to reduce activity. [ABSTRACT FROM AUTHOR]

Vezikoureterální reflux (VUR) patří mezi nejčastější vrozené vývojové vady uropoetického traktu. VUR je diagnostikován a léčen více jak 50 let. Během této doby byla získána řada informací a zkušeností, které v poslední době změnily přístup k diagnostice a léčbě VUR. Zavedení prenatálního ultrazvukového screeningu umožňuje indikovat mikční cystouretrografii (MCUG) záhy po porodu a diagnostikovat tak VUR časně, ještě před prodělanou infekcí močových cest (IMC). U řady pacientů, kteří jsou diagnostikováni časně, je prokázáno závažné poškození ledvinného parenchymu, aniž by prodělali IMC; tito pacienti s největší pravděpodobností trpí vrozenou dysplazií ledvin. Poslední ranodmizované studie ukazují, že získané poškození ledvin při VUR je méně časté, než se dříve předpokládalo a že je zde výrazný rozdíl mezi chlapci a děvčaty. Nové poškození ledvin je mnohem častěji diagnostikováno u děvčat, obzvlášť v případě recidivujících IMC. Tyto skutečnosti by měly vést k individualizaci diagnostiky a léčby VUR s cílem snížit počet invazivních vyšetření a současně ale zabránit v maximální možné míře novému poškození ledvinného parenchymu. Zlatým standardem diagnostiky VUR je MCUG, která by měla být indikována u pacientů s antenatálně diagnostikovanou závažnou ureterohydronefrózou, u pacientů s recidivujícími febrilními IMC. Pacienti, kteří prodělají první horečnatou IMC, by měli být podrobeni MCUG pouze v případě abnormálního ultrazvukového nálezu, nebo v případě komplikovaného průběhu IMC. V léčbě VUR se stále uplatňuje dlouhodobá antibiotická profylaxe. Chirurgická léčba (reimplantace ureteru, endoskopická léčba) by měla být vyhrazena pro pacienty s nejvyšším stupněm refluxu a pro pacienty, kteří prodělají IMC přes antibiotickou profylaxi. [ABSTRACT FROM AUTHOR]