A 13-year patient journey of infant giant clival chordoma: case report and literature review.

Chordomas are rare malignant bone tumours that develop from the ectopic remnants of the embryonic notochord. In contrast to adults, the majority in children under 16 present intra-cranially (63%). In 2006, we reported the youngest case of a large clival chordoma, a 15-week old baby, the second case to present without skull base involvement and the fourth case of chordoma in a patient with tuberous sclerosis (TS) Kombogiorgas (Childs Nerv Syst 22(10):1369-1374, 2006). In this report, we provide an update on this patient's journey through a range of therapeutic options and summarize an update of the literature, since 2006, for this patient group.

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.

Effectiveness of a social support intervention on infant feeding practices: randomised controlled trial.

BACKGROUND: To assess whether monthly home visits from trained volunteers could improve infant feeding practices at age 12 months, a randomised controlled trial was carried out in two disadvantaged inner city London boroughs. METHODS: Women attending baby clinics with their infants (312) were randomised to receive monthly home visits from trained volunteers over a 9-month period (intervention group) or standard professional care only (control group). The primary outcome was vitamin C intakes from fruit. Secondary outcomes included selected macro and micro-nutrients, infant feeding habits, supine length and weight. Data were collected at baseline when infants were aged approximately 10 weeks, and subsequently when the child was 12 and 18 months old. RESULTS: Two-hundred and twelve women (68%) completed the trial. At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients. At first follow-up, however, infants in the intervention group were significantly less likely to be given goats' or soya milks, and were more likely to have three solid meals per day. At the second follow-up, intervention group children were significantly less likely to be still using a bottle. At both follow-up points, intervention group children also consumed significantly more specific fruit and vegetables. CONCLUSIONS: Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55500035.

The diagnosis of preschool bipolar disorder presenting with mania: open pharmacological treatment.

BACKGROUND: Diagnosis of bipolar disorder (BPD) in preschool children is controversial, although preliminary data suggest that children with BPD may present with classic manic symptoms in a more chronic, rapid cycling presentation. While children with BPD are extremely dysfunctional, presenting symptoms and symptom expression remains to be further defined. Clarification of the presentation of BPD in children could result in better treatment. METHODS: Thirty-one patients, ages 2-5 years, were identified by chart review of all children treated at our pediatric bipolar clinic. All available historical, symptom, and treatment information was collected and summarized. RESULTS: Patients were approximately 2:1 male: female, predominantly Caucasian, with an average age of symptom onset of 3 years. Most frequent presenting symptoms (100%) included irritability, increased energy, and aggression. Prominent symptoms (>80%) included euphoria, grandiosity, decreased need for sleep, pressured speech, and distractibility. Eighty percent of patients had concurrent Attention-Deficit Hyperactivity Disorder (ADHD). Twenty-one of the 31 patients reported prior treatment attempts with either a stimulant or antidepressant without the protective benefit of a mood stabilizer, and of these, 13 (62%) reported a worsening of mood symptoms during that treatment period. Twenty-six of 31 were initially treated in our clinic openly with a mood stabilizer, primarily valproic acid, with a significant decrease in manic symptoms (p=0.03) following initial treatment. Long-term treatment demonstrated continued improvements from baseline (p=0.01). LIMITATIONS: The retrospective design of this study limits the conclusions that can be drawn. Due to the lack of a formal protocol, treatment was open and based on clinical judgment on an individual case basis. CONCLUSIONS: The symptom expression in these patients allowed for diagnosis according to DSM-IV criteria. Treatment with mood stabilizers was clinically effective, with corresponding significant developmental benefits.

Fluid flow and reactive transport around potential nuclear waste emplacement tunnels at Yucca Mountain, Nevada.

The evolution of fluid chemistry and mineral alteration around a potential waste emplacement tunnel (drift) is evaluated using numerical modeling. The model considers the flow of water, gas, and heat, plus reactions between minerals, CO(2) gas, and aqueous species, and porosity-permeability-capillary pressure coupling for a dual permeability (fractures and matrix) medium. Two possible operating temperature modes are investigated: a "high-temperature" case with temperatures exceeding the boiling point of water for several hundred years, and a "low-temperature" case with temperatures remaining below boiling for the entire life of the repository. In both cases, possible seepage waters are characterized by dilute to moderate salinities and mildly alkaline pH values. These trends in fluid composition and mineral alteration are controlled by various coupled mechanisms. For example, upon heating and boiling, CO(2) exsolution from pore waters raises pH and causes calcite precipitation. In condensation zones, this CO(2) redissolves, resulting in a decrease in pH that causes calcite dissolution and enhances feldspar alteration to clays. Heat also enhances dissolution of wall rock minerals leading to elevated silica concentrations. Amorphous silica precipitates through evaporative concentration caused by boiling in the high-temperature case, but does not precipitate in the low-temperature case. Some alteration of feldspars to clays and zeolites is predicted in the high-temperature case. In both cases, calcite precipitates when percolating waters are heated near the drift. The predicted porosity decrease around drifts in the high-temperature case (several percent of the fracture volume) is larger by at least one order of magnitude than in the low temperature case. Although there are important differences between the two investigated temperature modes in the predicted evolution of fluid compositions and mineral alteration around drifts, these differences are largely within to the model uncertainty and the variability of water compositions at Yucca Mountain.

A novel device for the rapid in-clinic measurement of haemoglobin A1c.

In order to evaluate a novel technique for measuring haemoglobin A1c using a cassette-based immunoassay method we have undertaken a laboratory evaluation using 48 patient samples and a separate within-clinic prospective study of 59 diabetic patients. Individuals were recruited from general (48 patients), paediatric (19 patients), obstetric (24 patients), and general practice (15 patients) diabetic clinics. Agreement was evaluated between HbA1c results obtained using the new method (AMES DCA 2000) and an established laboratory assay (DIAMAT HPLC system). The mean differences between the two results (AMES DCA 2000-DIAMAT) (95% confidence intervals) were: laboratory -0.69% (-1.42 to 0.04%); paediatric clinic -0.93% (-1.93 to 0.07%); obstetric clinic -0.29% (-1.09 to 0.51%), and general practice clinic -0.77% (-1.3 to -0.24%). For the AMES DCA 2000, the coefficient of variation for HbA1c of 5.2% was 1.6% and for HbA1c of 13%, 2.4%. This instrument was used without difficulty by four different operators. Intra-assay coefficient of variation for each operator was < 3.4%. In 9/18 patients where a specific assessment of clinical utility was made, knowledge of the HbA1c result at the time of consultation lead to a change in treatment. Methodology of this type may be used successfully within a diabetic clinic setting in both primary care and hospital environments.