Hydrocephalus in children under the age of five from diagnosis to short-/medium-/long-term progression: a retrospective review of 142 children

The aim of this study is to evaluate the clinical history and prognosis of children with early-onset hydrocephalus. The retrospective study’s inclusion criteria were hydrocephalus diagnosis before the age of 5 years, independent of aetiology, and birth details, January 1, 2000 to December 31, 2014. Overall, 142 children were entered into the study, divided into 11 aetiological groups: premature-birth post-intraventricular haemorrhage (16%), brain tumours (16%), spina bifida (15%), aqueductal stenosis (8%), post-meningitis (8%), post-haemorrhage (8%), Dandy–Walker malformation (6%), unknown origin (6%), arachnoid cyst (5%), miscellaneous obstruction (4%), and various causes (8%). In total, 23 patients died, primarily from the tumour group. Ventriculostomy, performed 42 times, was successful in 20 patients. Overall, 226 internal shunts were placed in 99 children. Infectious complications affected 19% of children after shunt placement and 51% after mechanical complications. Mean follow-up was 4 years 10 months, with 61% of children progressing fairly well, especially those with aqueductal stenosis, cysts, and unknown or diverse obstructive causes. Post-meningitis hydrocephalus displayed the poorest outcome. Isolated obstructive hydrocephalus exhibited better prognosis, with most obstructive aetiologies effectively treated via ventriculostomy. Children treated by shunt placement were more at risk of complications. Aetiologies with associated abnormalities and neurological sequelae had poorer outcomes.     

Nuclear imaging of thrombosis in small animal

Thromboembolic disorders are a major cause of morbidity and mortality worldwide. The progress in noninvasive imaging techniques has led to the development of radionuclide imaging based on SPECT and PET approaches to observe molecular and cellular processes that may underlie the onset and progression of disease. The advantages of using normal and genetically modified small animal research have spurred the development of dedicated small animal imaging systems. Animal models of venous and arterial thrombosis are largely used and have improved our understanding of the etiology and pathogenesis of thrombosis. Here, we review the literature regarding nuclear imaging of thrombosis in mice and rats.     

Reliability and efficacy of a new CO<Subscript>2</Subscript> laser hollow fiber: a prospective study of 39 patients

We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40WG CO₂ laser with the FiberLase flexible waveguide (CO₂ LWG) (Lumenis, Santa Clara, CA) with the objective to test its reliability and efficacy. Patients older than 18 years, with oral, pharyngo-laryngeal or tracheal benign or premalignant lesions were enrolled after signing an informed consent. This prospective study was conducted between October 2010 and May 2011 in two tertiary care university hospitals. Thirty-nine patients were enrolled in the study. The mean age was 47.9 years (range 18–86 years). There were 21 women and 18 men. Thirteen patients had hypertrophy of lymphoid tissue (palatine and or lingual), nine patients had granulomas, four patients had an exudative glottic lesion, three patients had severe dysplasia (glottic and supraglottic), three patients had leukoplakia, two patients had glottal cysts, two patients had laryngeal papilloma, two patients had bilateral paralysis of the vocal folds and one patient suffered from spasmodic dysphonia. Eighty-two percent of the procedures were performed under general anesthesia with laryngo-tracheal intubation. The CO₂ fiber passed through a handpiece was used with a microscope in the majority of the procedures. The laser delivery mode parameter used was: SuperPulse or Continuous Wave. Power levels were 3–15 Watts (W), continuous delivery. Each procedure utilized one CO₂ fiber which performed adequately throughout the procedure. No complications were noted with the use of this technology. A bipolar cautery was needed to control bleeding in eight procedures; all these procedures were tonsillectomies. The CO₂ LWG is a safe and reliable tool for TLS. It is durable enough to last through the entire surgical procedure without the need for replacement. Its use must be tailored depending on the type and location of the lesion, the CO₂ lasers tissue effects as well as the surgeon’s experience.     

Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of Caucasian non-smokers

EML4-ALK adenocarcinomas constitute a new molecular subgroup of lung tumours that respond very well to crizotinib, an ALK inhibitor. However, the diagnosis of ALK rearrangement in lung cancer is challenging. The aim of this study was to compare the diagnostic accuracy of five different methods in a series of 20 EGFR(wt/wt) lung adenocarcinomas from non- or light- smokers. Multiplex RT-PCR was considered as gold standard and identified four ALK-rearranged tumours among the 20 tested tumours. qRT-PCR got an interpretability rate of 100% and accurately typed all 20 tumours. qRT-PCR from corresponding formalin-fixed paraffin-embedded (FFPE) specimens got an interpretability rate of 65%. Out of the four previously identified ALK-rearranged cases, three were interpretable and two were retrieved using FFPE qRT-PCR. ALK break-apart FISH got an interpretability rate of 60% and accurately typed all of the twelve remaining cases. Anti-ALK immunohistochemistry (IHC) accurately typed all twenty tumours using a cut-off value of strong staining of 100% tumour cells. The 16 non ALK-rearranged tumours got no/light staining in 13 cases, and a moderate staining of 80-100% tumour cells in 3 cases. We then analysed four solid signet-ring lung adenocarcinomas. FFPE qRT-PCR, FISH and immunohistochemistry were concordant in three cases, with positive and negative results in respectively one and two cases. The fourth case, which was positive by FISH and immunohistochemistry but negative by RT-PCR, was shown to have a non-EML4-ALK ALK-rearrangement. As various factors such as RNA quality, fixation quality and type of ALK rearrangement may impede ALK screening, we propose a combined FISH/molecular biology diagnostic algorithm in which anti-ALK immunohistochemistry is used as a pre-screening step.     

Low-frequency stimulation induces a new form of LTP, metabotropic glutamate (mGlu5) receptor- and PKA-dependent, in the CA1 area of the rat hippocampus

Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with 60-electrode recording array. Remarkably, the application of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in the induction of a slow-onset long-term potentiation (LTP) in the immediate vicinity of the stimulated electrode. This phenomenon was observed exclusively in the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. The induction of this slow-onset LTP required neither N-methyl-D-aspartate (NMDA) nor non-NMDA ionotropic receptor activation but was strongly dependent on metabotropic glutamate mGlu(5) receptor stimulation and [Ca(2+)]i increase. In addition, this form of synaptic plasticity was associated with an increase in cAMP concentration and required protein kinase A activation. Paired-pulse facilitation ratio and presynaptic fiber volley amplitude were unaffected when this LTP was triggered, suggesting the involvement of postsynaptic modifications. Although mitogen activated protein kinase pathway was stimulated after the application of low frequency, the induction and maintenance of this slow-onset LTP were not dependent on the activation of this intracellular pathway. The direct activation of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying similar features. This new form of LTP could represent the mnesic engram of mild and repetitive stimulation involved in latent learning.     

Safety assessment of intensive induction therapy in childhood anaplastic large cell lymphoma: report of the ALCL99 randomised trial

Background

ALCL99 protocol including six courses of chemotherapy derived from the NHL‐BFM protocol is widely used for the treatment of paediatric anaplastic large‐cell lymphoma. In the ALCL99 trial, patients were randomised to receive MTX 1 g/m² in 24 hr with intrathecal injection (MTX1) versus MTX 3 g/m² in 3 hr without intrathecal (MTX3); then to receive or not vinblastine (high‐risk patients). The present study provides information about the acute adverse reactions (ARs) during the six courses of the ALCL99 treatment, assesses risk factors for ARs and evaluates the risk of overweight related to treatment.

Methods

Data concerning ARs were assessed using CTCv2 and analysed overall and according to the type of course.

Results

Between 1999 and 2005, 352 patients were recruited. Toxicity assessed after 2050 courses included grade 4 neutropaenia (70% of courses), grade 3–4 stomatitis (13%), grade 3–4 transaminase elevation (10%) and grade 3–4 infection (5%). Four patients (1%) died of toxicity. The toxicity profile differed between courses‐A (significantly more haematological toxicity) and courses‐B (significantly more stomatitis). The percentage of ARs was higher after the first course than after subsequent courses. Severe toxicity was more frequent after MTX1 than after MTX3 courses but did not differ between courses with or without vinblastine. Overall 20% of patients had a weight gain exceeding 20%.

Conclusions

The high rate of acute toxicity should be considered when using the ALCL99 protocol. Chemotherapy including MTX 3 g/m² in 3 hr was less toxic than the same regimen with MTX 1 g/m² in 24 hr. Adding vinblastine did not increase the risk of toxicity. Pediatr Blood Cancer 2011;56:1071–1077. © 2011 Wiley‐Liss, Inc.