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J Gillis

Publications and source records attributed to J Gillis.

At least 19 recordsLinked to original sources

Spontaneous rhythmic field potentials of isolated mouse hippocampal-subicular-entorhinal cortices in vitro.

The rodent hippocampal circuit is capable of exhibiting in vitro spontaneous rhythmic field potentials (SRFPs) of 1-4 Hz that originate from the CA3 area and spread to the CA1 area. These SRFPs are largely correlated with GABA-A IPSPs in pyramidal neurons and repetitive discharges in inhibitory interneurons. As such, their generation is thought to result from cooperative network activities involving both pyramidal neurons and GABAergic interneurons. Considering that the hippocampus, subiculum and entorhinal cortex function as an integrated system crucial for memory and cognition, it is of interest to know whether similar SRFPs occur in hippocampal output structures (that is, the subiculum and entorhinal cortex), and if so, to understand the cellular basis of these subicular and entorhinal SRFPs as well as their temporal relation to hippocampal SRFPs. We explored these issues in the present study using thick hippocampal-subicular-entorhinal cortical slices prepared from adult mice. SRFPs were found to spread from the CA1 area to the subicular and entorhinal cortical areas. Subicular and entorhinal cortical SRFPs were correlated with mixed IPSPs/EPSPs in local pyramidal neurons, and their generation was dependent upon the activities of GABA-A and AMPA glutamate receptors. In addition, the isolated subicular circuit could elicit SRFPs independent of CA3 inputs. We hypothesize that the SRFPs represent a basal oscillatory activity of the hippocampal-subicular-entorhinal cortices and that the subiculum functions as both a relay and an amplifier, spreading the SRFPs from the hippocampus to the entorhinal cortex.

Action Potentials↗

Outcome of children with neuromuscular disease admitted to paediatric intensive care.

AIMS: To determine the outcome of children with neuromuscular disease (NMD) following admission to a tertiary referral paediatric intensive care (PICU). METHODS: All children with chronic NMD whose first PICU admission was between July 1986 and June 2001 were followed up from their first PICU admission to time of study. The outcomes recorded were death in or outside of PICU, duration of PICU admission, artificial ventilation during admission and following discharge from PICU, and readmission to PICU. RESULTS: Over 15 years, 28 children were admitted on 69 occasions. Sixteen (57%) children had more than one admission. The median duration of PICU admission was 4 days (range 0.5-42). Twenty three per cent of unplanned admissions resulted in the commencement of respiratory support that was continued after discharge from the PICU. Severity of functional impairment was not associated with longer duration of stay or higher PRISM scores. Ten children (36%) died, with four (14%) deaths in the PICU. A higher proportion of children with severe limitation of function were among children that died compared to survivors. CONCLUSION: Most children with NMD admitted to the PICU recover and are discharged without the need for prolonged invasive ventilation. However, in this group of children, the use of non-invasive home based ventilation is common and they are likely to require further PICU admission.

Adolescent↗

The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes.

Expression of the src homology 3 (SH3) domain-containing expressed in tumorigenic astrocytes (SETA) gene is associated with the tumorigenic state in astrocytes. SETA encodes a variety of adapter proteins containing either one or two SH3 domains, as suggested by the sequence heterogeneity of isolated cDNAs. Using both SH3 domains in a yeast two-hybrid screen of a glial progenitor cell cDNA library, we isolated the rat homolog of the ALG-2-interacting protein 1 or ALG-2-interacting protein X (AIP1/Alix). In vitro confrontation experiments showed that the SH3-N domain of SETA interacted with the proline-rich C terminus of AIP1. In co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-linked gene 2 protein. Endogenous SETA and AIP1 proteins showed similar patterns of staining in primary rat astrocytes. Misexpression of a variety of SETA protein isoforms in these astrocytes revealed that they localized to the actin cytoskeleton. Furthermore, SETA proteins containing the SH3-N domain were able to sensitize astrocytes to apoptosis induced by UV irradiation. Expression of the isolated SH3-N domain had the greatest effect in these experiments, indicating that interference in the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to DNA damage.

Actins↗

A taste of honey.

Infantile botulism classically presents with a triad of clinical features: Bulbar palsies (slow/absent pupil response) Alert Absent fever Other common features are: Constipation, ptosis and poor feeding The diagnosis is a clinical one, confirmed by EMG and by testing stool for the organism, C. botulinum, or its toxin. Parents should be advised not to dip pacifiers in honey. In future Botulinum Immune Globulin may be available and should be considered if further trials are published showing benefit. Nosocomial infections, such as RSV, are important and should be carefully avoided, particularly in patients recovering from botulism.

Botulism↗

Improved outcomes of children with malignancy admitted to a pediatric intensive care unit.

OBJECTIVE: To assess the acute and long-term outcomes of children admitted to the intensive care unit with cancer or complications after bone marrow transplantation. DESIGN: Retrospective analysis of databases from a prospective pediatric intensive care unit (PICU) database supplemented by case notes review. SETTING: A PICU in a tertiary pediatric hospital. PATIENTS: All children with malignancy admitted to the PICU between May 1, 1987, and April 30, 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 206 admissions to the PICU during a 9-yr study period of 150 children with malignancies or complications after bone marrow transplantation. Forty patents died in the PICU (27% mortality rate). The most frequent indications for PICU admission were shock and respiratory disease. Of 56 children admitted with shock, there were 16 deaths (29% mortality rate). In 24 episodes of sepsis, inotropic and ventilatory support were required and 13 patients (54%) survived. Analysis of long-term survival gave estimates of 50% survival for all oncology patients admitted to the PICU and 42% for those admitted for shock. CONCLUSIONS: A high proportion of oncology patients admitted to the PICU requiring intensive intervention survive and go on to be cured of their malignancy. Our study suggests the PICU outcome for these patients has improved.

Adolescent↗

Malignant transformation of p53-deficient astrocytes is modulated by environmental cues in vitro.

The early incidence of p53 mutation in astrocytomas suggests that it plays an important role in astrocyte transformation. Astrocytes isolated from homozygous p53 knockout mice grow rapidly, lack contact inhibition, and are immortal. Here we tested whether the loss of p53 is sufficient for progression to tumorigenicity of astrocytes. We grew primary astrocytes under three conditions for over 120 population doublings and assessed their antigenic phenotype, chromosome number, and expression of glioma-associated genes as well as their ability to form colonies in soft agarose and tumors s.c. and intracranially in nude mice. Under two conditions (10% FCS and 0.5% FCS plus 20 ng/ml EGF), cells acquired the ability to form colonies in soft agarose and tumors in nude mice, and this was accompanied by the expression of genes, including epidermal growth factor receptor, platelet-derived growth factor receptor alpha and beta, protein kinase Cdelta, and vascular endothelial growth factor, which are known to be aberrantly regulated in human astrocytomas. Under the third condition (0.5% FCS plus 10 ng/ml basic fibroblast growth factor), astrocytes gained the ability to form colonies in soft agarose and had abnormal chromosome numbers similar to cells in the first two conditions but did not form tumors in nude mice or overexpress glioma-associated genes. These data provide experimental evidence for the idea that the malignant progression initiated by the loss of p53 may be subject to modulation by extracellular environmental influences.

Aneuploidy↗

Indirect calorimetry in mechanically ventilated children: a new technique that overcomes the problem of endotracheal tube leak.

OBJECTIVES: To develop indirect calorimetry to enable measurement of energy expenditure in mechanically ventilated children and to assess the effect of endotracheal tube leak on the accuracy of indirect calorimetry measurements. DESIGN: Prospective, observational study, using a convenience sample. SETTING: Tertiary pediatric intensive care unit in a university-associated children's hospital. PATIENTS: Eighteen patients, 3 months to 10 yrs of age, with various diagnoses, and requiring mechanical ventilation. INTERVENTIONS: Patients were intubated and received routine intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Energy expenditure and respiratory quotient were measured using a new modification to the technique of indirect calorimetry, which includes an assessment of any expired gas lost around the endotracheal tube. Mean energy expenditure was 97% of predicted energy expenditure, but there was great variability between patients, and energy expenditure could not be estimated reliably from predictive equations. The amount of expired gas lost because of gas leak around the endotracheal tube was often a clinically important proportion of total expired gas, and this lost gas could not be predicted by audible endotracheal tube leak. CONCLUSIONS: Measurement of energy expenditure by indirect calorimetry may be useful in the nutritional management of critically ill children. Results may be inaccurate if the gas lost because of leak around uncuffed endotracheal tubes is not taken into account.

Calorimetry, Indirect↗

Inferior vena cava thrombosis as a complication of femoral vein catheterisation.

Indwelling femoral venous catheters were prospectively studied by ultrasonography to define the frequency and evolution of inferior vena cava (IVC) thrombosis. IVC thrombosis was identified in six of 56 catheters (54 children). Only one patient with a positive ultrasound scan had clinical signs of thrombosis. All children with IVC thrombosis had had catheters in place for over six days. It is recommended that either the femoral central venous catheters are routinely changed at six days or ultrasound studies are routinely performed twice a week in all patients with catheters in situ for six or more days and that the catheter is removed immediately if evidence of thrombosis appears.

Catheterization, Central Venous↗

Continuous venovenous haemofiltration in the acute treatment of inborn errors of metabolism.

The accumulation of toxic metabolites in children with inborn errors of metabolism may cause acute metabolic crises and result in long-term neurological dysfunction or death. Peritoneal dialysis often provides insufficient clearance to protect against these complications, while intermittent haemodialysis cannot prevent reaccumulation of metabolites between dialysis sessions. We describe the use of continuous venovenous haemofiltration (CVVH) or haemodiafiltration (CVVHD) in three infants with maple syrup urine disease (MSUD) and one child with carbamyl phosphate synthetase (CPS) deficiency. All children with MSUD had a satisfactory reduction in branched-chain amino acids within 24 h of onset of haemofiltration, and are now neurologically normal. The child with CPS deficiency had an ammonia level of < 100 mumol/l within 24 h of onset of therapy, but died 3 days later from unrelated cardiovascular complications. Complications of the therapy included the clotting of one haemofilter and the replacement of two vascular access catheters per patient on average per therapy. Two patients required blood transfusion. We report the successful use of CVVH and CVVHD in the acute management of metabolic crises associated with inborn errors of metabolism, and believe that these may be the optimal techniques for the acute clearance of toxic metabolites.

Acute Disease↗

Lumbar punctures in suspected bacterial meningitis: too many or too few?

Children aged 1 month to 14 years admitted to the Royal Alexandria Hospital for Children during a 10 month period with suspected meningitis were studied prospectively. The aims were to determine how often lumbar puncture (LP) was delayed or never done, in relation to the outcome of all children, in order to determine the risks of LP and the risks of not doing LP. Of 218 children with suspected meningitis, LP was performed immediately in 195 (89.4%). Meningitis was diagnosed in 49 of these (bacterial 18, viral 31). No child developed cerebral herniation due to immediate LP. There were 11 traumatic taps and two children required repeated attempts. Lumbar puncture was delayed, but performed at a later time in 17 children, of whom three had proven bacterial meningitis, 1 had presumed bacterial meningitis but no organism was detected and 13 had alternative diagnoses. Six children never had an LP, although ventricular cerebrospinal fluid was obtained from two. Four of these six children had presumptive bacterial meningitis, one had tuberculous meningitis presenting with acute hydrocephalus and diagnosed post-mortem, and one had a very poor neurological outcome and no final diagnosis was reached. Of the 27 children with bacterial meningitis, LP was performed immediately in 18, or two-thirds. There were only minor adverse effects of immediate LP. Delayed LP probably resulted in failure to identify the organism in one child with bacterial meningitis, but did not adversely affect outcome in any child. Of the six children in whom LP was never performed, in only one was no final diagnosis reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Familial asplenia.

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Bacterial Infections↗

Tumor IGF-II content in a patient with a colon adenocarcinoma correlates with abnormal expression of the gene.

We have recently reported abnormal insulin-like growth factor-II (IGF-II) mRNA levels in a number of human colorectal adenocarcinomas. Using an IGF-II radioimmunoassay, we have now detected high levels of both 10-kDa and 7.5-kDa IGF-II species (2,370 ng/g) in a right colon tumor showing a 800-fold IGF-II gene over-expression in comparison to the normal adjacent tissue. The higher-molecular-mass form represents 74% of the total immunoreactive IGF-II detected in the tumor. This form appears to be less reactive in the radioreceptor assay than in the radioimmunoassay. The insulin-like growth factor-I (IGF-I) concentration in the tumor is low. The patient's pre-operative serum IGF-II level is not increased and the proportion of the 10-kDa species is normal. In addition, the IGF-II/IGF-I ratio is 3 in the serum and 308 in the tumor. Our results show that the very high IGF-II level produced by the tumor does not influence the seric concentration of the growth factor.

Adenocarcinoma↗

Review of intubation in severe laryngotracheobronchitis.

Of 208 children who required relief of severe airway obstruction due to laryngotracheobronchitis by an artificial airway (nasotracheal intubation or tracheostomy) during a 10-year-period, 181 (87%) were intubated and later extubated. Twenty-seven children (13%) had tracheostomies performed. The tracheostomies were for severe subglottic narrowing precluding the passage of an adequate size endotracheal tube in 10 children, and for severe endotracheal tube trauma in 17 children. Five children developed acquired subglottic stenosis (2.4% of 208) and 1 of these has a retained tracheostomy. One child died of cardiac disease. The remaining 202 children had no long-term complications of laryngotracheobronchitis, intubation, or tracheostomy. It is concluded that nasotracheal intubation is a satisfactory artificial airway for laryngotracheobronchitis. Endoscopic evaluation in a selected group of these children will identify those with significant intubation trauma or severe subglottic narrowing in whom continued intubation may cause permanent subglottic damage. The low incidence of acquired subglottic stenosis in this series supports the practice of selective endoscopy and tracheostomy.

Airway Obstruction↗

Entrapment.

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Child↗