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Biomedical subjects

S Cunningham

Publications and source records attributed to S Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bronchoconstriction following nebulised colistin in cystic fibrosis.

Nebulised colistin is regularly used as antipseudomonal therapy in children with cystic fibrosis. We assessed bronchoconstriction in response to nebulised colistin in 58 children. Nebulised colistin significantly reduced FEV(1), MEF(25%), and SaO(2) for 15 minutes. In 20 children the reduction was greater than 10% from baseline FEV(1), and was still at that level in five at 30 minutes. Subjective assessment, baseline FEV(1), and serum IgE were unable to identify susceptible children. It is recommended that children receiving colistin should be carefully assessed for bronchoconstriction.

Administration, Inhalation↗
PubMed2000

A gene therapy approach to enhance the targeted radiotherapy of neuroblastoma.

BACKGROUND: The aims of this study were to determine whether the introduction and expression of the noradrenaline transporter (NAT) gene into NAT-negative neuroblastoma cell lines would make them amenable to targeted radiotherapy using [(131)I]MIBG. PROCEDURE: Neuroblastoma cell lines were transfected with a eukaryotic expression vector containing the bovine noradrenaline transporter cDNA under the expression of the CMV promoter. Stable transfectants were created by selection in geneticin (G418) and were characterised for their MIBG uptake ability and susceptibility to [(131)I]MIBG therapy. RESULTS: The cell line SK-N-MC, which normally shows no ability to take up MIBG, was successfully transfected with bNAT. SK-N-MC.bNAT transfectants exhibited uptake and release kinetics similar to those of the natural NAT-expressing cell line SK-N-BE(2c). Levels of [(131)I]MIBG uptake were 33% of those of the highest naturally NAT-expressing cell line SK-N-BE(2c). Growth delay assays using multicellular spheroids indicated that this degree of [(131)I]MIBG uptake was sufficient to inhibit growth at radioactive concentrations of 4 Mbq/ml. CONCLUSIONS: These results demonstrate the feasibility of combining gene therapy with targeted radiotherapy to enhance uptake, and hence radiation dose, to neuroblastoma tumours using [(131)I]MIBG. With the appropriate delivery vehicle and tumour-specific control of expression, the introduction of noradrenaline transporter molecules may be a viable means of enhancing the response of neuroblastoma tumours to [(131)I]MIBG therapy.

Carrier Proteins↗
PubMed2000

Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis.

Identifying noninvasive markers of pulmonary inflammation would be useful in assessing new therapies in children. Breath condensate is a simple and potentially acceptable sample medium even in small children. The technique has previously been used in adults, but not children with cystic fibrosis. The technique was assessed in 36 children with cystic fibrosis (mean age 10.4 yrs) and 17 control subjects, analysing samples for nitrite, interleukin(IL)-8 and salivary and nasal contamination. Correlations were made between levels of the inflammatory markers and forced expiratory volume in one second/forced vital capacity, chest radiograph score and use of inhaled steroids. On samples without significant contamination (<10 u x L(-1) amylase) nitrite was detected in 93% of samples at a median concentration of 3.0 microM compared with 50% of control samples at a median of 0.5 microM. Condensate amylase levels did not correlate with the nitrite value obtained (r=0.31). IL-8 was detected in 33% of CF samples. Breath condensate is an acceptable method of sample collection in children. Nitrite was raised in breath condensate from patients with cystic fibrosis when compared with control subjects.

Breath Tests↗
PubMed2000

An evaluation of active shape models for the automatic identification of cephalometric landmarks.

This paper describes an evaluation of the application of active shape models to cephalometric landmarking. Permissible deformations of a template were established from a training set of hand-annotated images and the resulting model was used to fit to unseen images. An evaluation of this technique in comparison to the accuracy achieved by previous methods is presented. Sixty-three randomly selected cephalograms were tested using a drop-one-out method. On average, 13 per cent of 16 landmarks were within 1 mm, 35 per cent within 2 mm, and 74 per cent within 5 mm. It was concluded that the current implementation does not give sufficient accuracy for completely automated landmarking, but could be used as a time-saving tool to provide a first-estimate location of the landmarks. The method is also of interest because it provides a framework for a range of future improvements.

Adolescent↗
PubMed2000

No-carrier-added 123I-MIBG: an initial clinical study in patients with phaeochromocytoma.

Radioiodinated meta-iodobenzylguanidine (MIBG) is used routinely for imaging and targeted radiotherapy of tumours derived from the neural crest. Since active uptake of MIBG by the noradrenaline transporter (NAT) makes a greater contribution to total drug accumulation than passive uptake when MIBG is present at low concentrations, tumour-specific uptake should be enhanced by the administration of lower molar amounts of MIBG. This could be achieved through the use of MIBG with a high specific activity. Commercially available preparations of 123I-MIBG have specific activities of approximately 200 MBq.mg-1. We have synthesized and used no-carrier-added (n.c.a.) 123I-MIBG produced by an iododesilylation reaction (specific activity 0.7 TBq.mg-1). We report here the first clinical studies comparing the commercially available and n.c.a. MIBG diagnostic preparations. Five patients with known phaeochromocytoma were studied. Unlike studies in animal models, no consistent improvement in tumour uptake was observed with the n.c.a. material. A larger patient group is required to determine whether there are significant differences between the two preparations, before proceeding to studies at therapeutic activity levels of n.c.a. 131I-MIBG. Even with no improvement in tumour uptake, n.c.a. MIBG may be the favoured formulation for therapeutic applications to reduce the molar amount of drug injected.

3-Iodobenzylguanidine↗
PubMed2000

Medical students' attitudes to caring for a young infant--can parenting a doll influence these beliefs?

AIM: To investigate whether attitudes to parenting were altered in final year medical students following a period spent caring for a simulated infant. METHODS: Seventy medical students during their paediatric attachment in the final year completed a questionnaire regarding personal childcare attitudes. Students attached to a teaching hospital were allocated a 24 hour time period to care for "Baby Think It Over" (BTIO), a computerised doll that simulates a 6 week old infant and records care given. The students then completed a second questionnaire assessing the impact of the experience. RESULTS: Forty nine per cent of students thought their advice regarding sick children was less valid than if they had their own children; 96% of students believed their approach to parents caring for young infants could be improved by caring for a 6 week old infant. All the students felt their lifestyle would be affected. Following the BTIO care period, 79% considered the experience straightforward, with 35% expressing a little more empathy and 15% a lot more empathy for parents as a result. Thoughts regarding impact on lifestyle were unaltered. Caring for BTIO, however, was not considered to be a realistic experience and overall not particularly useful. CONCLUSION: Simulated infants are of only limited value in increasing medical student understanding of parental concerns.

Adult↗
PubMed2000

Total serum cholesterol in relation to psychological correlates in parasuicide.

BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS: To examine the relationship between total serum cholesterol and psychological parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups. RESULTS: Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.

Adolescent↗
PubMed2000

Clinical diagnosis of pneumothorax is late: use of trend data and decision support might allow preclinical detection.

Pneumothorax in the newborn has a significant mortality and morbidity. Early diagnosis would be likely to improve the outlook. Forty-two consecutive cases of pneumothorax that developed after admission to a tertiary referral neonatal medical intensive care unit over 4 y from 1993 to 1996 were reviewed. The time of onset of the pneumothorax was determined by retrospective evaluation of the computerized trend of transcutaneous carbon dioxide (tcpCO2) and oxygen tensions. The timing of the occurrence in the notes and x-rays determined the time of clinical diagnosis noted at the time. The difference was the time the condition was undiagnosed. The overall mortality before discharge was 45% (19 cases), four patients succumbing within 2 h. The median time (range) between onset of pneumothorax and clinical diagnosis was 127 min (45-660 min). In most cases, the endotracheal tube was aspirated and the transcutaneous blood gas sensor was repositioned, and in at least 40% of the cases, the baby was reintubated before the diagnosis was made. Reference centiles were constructed for level of tcpCO2 and slope of the trended tcpCO2 over various time intervals (in minutes) from 729 infants from 23 to 42 wk gestation who needed intensive care during the first 7 d of life from the same time period. The 5-min tcpCO2 trend slopes were compared in index and matched control infants. The presence of five consecutive and overlapping 5-min slopes greater than the 90th centile showed good discrimination for a pneumothorax (area under the receiver operating characteristic curve, 89%). We concluded that 1) the clinical diagnosis of pneumothorax was late, occurring when infants decompensate; 2) trend monitoring of tcpCO2 might allow the diagnosis to be made earlier if used properly; and 3) use of reference centiles of the trended slopes of tcpCO2 might be used for automatic decision support in the future.

Carbon Dioxide↗
PubMed2000

Hyperprolactinaemia: analysis of presentation, diagnosis and treatment in the endocrine service of a general hospital.

The charts of 184 patients with clinically significant hyperprolactinaemia who presented to a teaching hospital between 1978-1995 were reviewed, 158 (86%) females and 26 (14%) males. Hyperprolactinaemia was due to a microadenoma or was idiopathic in 36.4%, drug induced in 16%, associated with a macroadenoma in 12%, due to epilepsy in 7%, with other causes each contributing 5% or less. The presenting symptoms were amenorrhoea in 64%, galactorrhoea in 40.5%, infertility in 15%, visual field defect in 9%, with impotence in 30% and, gynaecomastia in 8% of men. One hundred and one patients were treated with bromocriptine (80%), surgery (35.4%) and radiotherapy (10.7%). Twenty-five percent of patients developed side-effects of bromocriptine for which cabergoline, a new long-lasting dopaminergic agonist, was successfully substituted. Presenting features responded to drug treatment in 70-80% of patients.

Bromocriptine↗
PubMed2000

A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat.

PURPOSE: To examine changes in the retinal vasculature of rat pups after 14 days of minute-by-minute small variations in oxygen. METHODS: Arterial oxygen data from a preterm infant who developed severe retinopathy of prematurity (ROP) was translated to equivalent values for the rat. Newborn rat pups were raised for 14 days in a cage in which a computer controlled the atmosphere to mimic the fluctuating oxygen profile (group V). Positive controls (P) of 12-hour cycles of 80% and 21% were run concurrently, as were room air controls (C). All were killed at day 14. RESULTS: Groups V and P had significantly larger avascular retinal areas than C [median, interquartile range (IQR) 1.7%, 0-7.9%; 10%, 8.1-13%; 0%, 0-0%, respectively; each group n = 30]. Group P had a higher capillary branch count than C (median, IQR: 310/mm(2); 253-311 mm(2); versus 277/mm(2), 272-364/mm(2), respectively), but this was not significant using a multilevel analysis. Group V had significantly reduced capillary counts compared with C (median, 261/mm(2); IQR, 215-290/mm(2); P < 0.05 multilevel analysis). No neovascularization was seen in any group, though abnormal terminal vessels were seen at the avascular/vascular retina interface in 73% of rats in group P and 21% of rats in group V. In situ hybridization on serial sections demonstrated VEGF in the inner nuclear layer of the retina in P and V, whereas C showed trace levels only. CONCLUSIONS: The vaso-obliterative stage of ROP can be induced in rats using clinically relevant oxygen levels.

Animals↗
PubMed1999

Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life.

OBJECTIVES: We aimed to: (1) assess the association of average, low, high and variable mean blood pressure (mbp) on death and the common morbidities of very low birthweight infants, and in doing so, (2) to derive representative reference ranges for mbp in very low birthweight infants. STUDY DESIGN: This five year retrospective study assessed 1 min computer recordings of intra-arterial mbp in 232 very low birthweight infants over the first 7 days of life in a tertiary NICU. Four measures of mbp were assessed: average, variability, maximum (per time period), and percentage of time with a mean blood pressure less than the infant's gestation. Correlation was made with death and the development of intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP). RESULTS: The mbp increased with increasing birthweight and postnatal age (though with a slight decrease on days 6 and 7). Birthweight, gestation and colloid support (adjusted for birthweight and gestation) were the only factors significantly associated with mbp. IVH was predominantly associated with a low and variable mbp on the day IVH was noted or the day before. PVL and ROP were not associated with blood pressure. CONCLUSIONS: These reference ranges include more infants and data than previously published and relate mbp in this cohort to morbidity and mortality. They could assist clinicians in judging appropriate mbp for birthweight.

Aging↗