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J M Littlewood

Publications and source records attributed to J M Littlewood.

At least 19 recordsLinked to original sources
PubMed1997

A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis.

Cystic fibrosis (CF) is a common, serious, inherited disease. The major cause of mortality in CF is lung disease, due to the failure of airway epithelial cells to express a functional product of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A potential treatment for CF lung disease is the expression of CFTR in the airways following gene transfer. We have undertaken a double-blinded, placebo-controlled, clinical study of the transfer of the CFTR cDNA to the nasal epithelium of 12 CF patients. Cationic liposomes complexed with plasmid containing the human CFTR cDNA were administered to eight patients, whilst four patients received placebo. Biopsies of the nasal epithelium taken 7 days after dosing were normal. No significant changes in clinical parameters were observed. Functional expression of CFTR assessed by in vivo nasal potential difference measurements showed transient correction of the CF chloride transport abnormality in two patients (15 days after dosing in one patient). Fluorescence microscopy demonstrated CFTR function ex vivo. In cells from nasal brushings. In total, evidence of functional CFTR gene transfer was obtained in six out of the eight treated patients. These results provide proof of concept for liposome-mediated CF gene transfer.

Adolescent↗
PubMed1996

The role of hepatobiliary scintigraphy in cystic fibrosis.

This was a prospective open study that examined the quantitative and qualitative analysis of hepatobiliary scintigraphy (DISIDA) in detecting liver involvement in cystic fibrosis (CF). Forty-four adult and pediatric patients (median age, 12.1 years; range, 1.1-36.3 years) were divided into three groups: group 1, no evidence of liver involvement (n = 8); group 2, biochemical evidence of liver involvement on two or more occasions (n = 26); and group 3, clinical evidence of liver disease (n = 10). In groups 1 and 2, the most common qualitative scintigraphic finding was focal intrahepatic retention of tracer (26/34 patients, 12 of whom had normal findings on ultrasonography). This finding corresponds to focal cholestasis and may warrant treatment with the choleretic agent ursodeoxycholic acid (UDCA). In the group 3 patients, the abnormal qualitative scintigraphic appearances (heterogeneous uptake of tracer and nodular liver outline) added little to the findings on ultrasonography; however, these patients had a prolonged mean hepatic clearance time compared with those in groups 1 and 2 (one-way ANOVA; P < .015). It is proposed that scintigraphy with DISIDA has a role in the detection of early liver involvement in cystic fibrosis.

Adolescent↗
PubMed1996

Role of anti-pseudomonal antibiotics in the emergence of Stenotrophomonas maltophilia in cystic fibrosis patients.

A retrospective case-control study of 12 patients positive for Stenotrophomonas maltophilia and 24 age-sex-matched controls revealed that in the year prior to initial isolation, colonised patients spent more days in hospital and received more days of oral ciprofloxacin, intravenous anti-pseudomonal antibiotics, and nebulised aminoglycosides. They were also more likely to have grown Pseudomonas aeruginosa at some time in the past, despite there being no difference in current chronic infection with this organism. The role of anti-pseudomonal antibiotics in promoting Stenotrophomonas maltophilia colonisation in cystic fibrosis is discussed.

Adolescent↗
PubMed1996

Pancreatin preparations used in the treatment of cystic fibrosis--lipase content and in vitro release.

BACKGROUND: Pancreatic extracts are essential in the treatment of the majority of cystic fibrosis patients. The clinical response to different preparations is often unpredictable and at present there is no sure method of determining the best preparation for a particular patient. METHODS: Creon, Nutrizym GR, Pancrease and the high-lipase versions, Creon 25,000, Nutrizym 22 and Pancrease HL, were investigated for lipase content and resistance to simulated gastric conditions. The rates of lipase release in response to pH change, bile salts and duodenal solids were investigated. The stability of lipase and its binding to duodenal solids were also investigated. RESULTS: Declared values for lipase content were exceeded in all preparations. All preparations were acid resistant. The release of lipase in response to pH change showed notable differences in release rates. After 20 min at pH 5.5, Creon released three times the amount of lipase compared with Pancrease, the other preparations coming within the range. Above pH 5.75, the release rates were comparable amongst the preparations. Bile salts influenced release variably whilst release in a solid-rich duodenal fluid was much slower than in buffers. The released lipase was susceptible to proteolysis and pH-dependent binding to duodenal solids; these effects may compromise lipolysis. CONCLUSIONS: These results show some factors contributing to variable clinical responses to pancreatic supplements. Improvements may result if a patient is assessed on different preparations.

Bile Acids and Salts↗
PubMed1995

Coeliac disease in childhood.

Coeliac disease usually presents in infancy or early childhood with diarrhoea, vomiting and interference with weight gain and growth. Withdrawal of dietary gluten is followed by resolution of the symptoms and signs and restoration of normal weight gain and growth; the characteristic subtotal villous atrophy of the jejunal mucosa also recovers. Later re-introduction of dietary gluten will lead to a return of the jejunal mucosal abnormality in the majority and to clinical relapse in many but not all. The severity and timing of both are variable and 5% of children initially considered on clinical, biopsy and gluten response evidence to have coeliac disease appear to develop permanent tolerance to gluten, although mucosal relapse may occur years after the re-introduction of dietary gluten in a minority, emphasizing the need for long-term follow-up. Although a diagnostic and subsequent follow-up jejunal biopsy are necessary to confirm the diagnosis, anti-gliadin IgA and IgG, anti-reticulum and anti-endomysium antibodies are now almost totally reliable in identifying children who have coeliac disease and are valuable in monitoring the adequacy of gluten withdrawal. Dietary compliance is frequently poor and regular supervision by a paediatric dietitian is needed; indeed, lifelong supervision to ensure gluten withdrawal is essential to reduce the chance of developing later gastrointestinal malignancy.

Adolescent↗
PubMed1995

Nebulised amiloride in respiratory exacerbations of cystic fibrosis: a randomised controlled trial.

OBJECTIVE: To assess the benefit of nebulised amiloride added to the standard inpatient treatment of a respiratory exacerbation in cystic fibrosis. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SUBJECTS: 27 cystic fibrosis patients (mean age 12.8 years). SETTING: Two hospitals in Leeds, UK. RESULTS: Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) showed improvements over the course of treatment, although there was no difference in respiratory function between the two groups at any of three time periods during the study. The time to reach peak FVC was significantly reduced in the amiloride group (4.2 v 7.6 days; 95% CI 0.4 to 6.4 days), but not in the time to reach peak FEV1 (5.7 v 7.9 days; 95% CI -1.2 to 5.6 days). CONCLUSIONS: Amiloride did not result in a greater overall improvement in respiratory function. There was a suggestion that it may have an effect on the rate of improvement, and thus may possibly influence the duration of treatment. This hypothesis deserves further evaluation.

Adolescent↗
PubMed1994

Aspergillus fumigatus colonisation and population density of place of residence in cystic fibrosis.

The relation between antibody titres of aspergillus in patients with cystic fibrosis and the population density of their place of residence was investigated. Patients with high titres of antibodies to Aspergillus fumigatus were significantly more likely to live in an area of low population density. Living in a rural environment may predispose to A fumigatus colonisation.

Antibodies, Fungal↗
PubMed1993

Cystic fibrosis in Asians.

The clinical course of cystic fibrosis in nine Pakistani Asians was compared with 18 non-Asian age and sex matched controls. The Asian patients grew Pseudomonas aeruginosa at an earlier age (4.0 v 7.5 years), tended to have lower respiratory function test results (forced vital capacity 58.5 v 76.8% predicted; forced expiratory volume in one second 79.8 v 100.3% predicted), and had significantly greater concentrations of immunoglobulin IgG (13.4 v 10.1 g/l). They had a lower weight for age (78.4 v 95.7%) and weight for height (90 v 98.5%) despite similar intakes of dietary energy. Four of the nine Asians carried the delta F508 mutation compared with 17 of 18 controls. All the Asian patients were born in the UK; seven of their mothers were born in Pakistan and had moderate or severe difficulties with the English language. It is concluded that Asian patients may have a more severe clinical course than matched controls and that genetic and environmental factors may be contributory.

Adolescent↗
PubMed1993

A double blind lipase for lipase comparison of a high lipase and standard pancreatic enzyme preparation in cystic fibrosis.

A standard acid resistant microsphere pancreatic enzyme preparation was compared with identical capsules half filled with mini-tablets of a new high lipase preparation in a randomised double blind crossover study in children with cystic fibrosis. Each patient received his/her usual number of capsules and the same dose of lipase during each period of the study. Eighteen patients completed the study. There were fewer gastrointestinal symptoms when pancreatic enzyme was supplied as the high lipase preparation. There was also a significant improvement in fat absorption (17%, 95% confidence interval (CI) 6 to 27), reduction in faecal fat output (15.8 g/day, 95% CI 6.4 to 22.5), and faecal energy loss (789 kJ/day, 95% CI 211 to 1384). It is concluded that half filled capsules of the new high lipase preparation are more effective than the standard preparation and it is likely that filled capsules would allow patients to use fewer than half the number of pancreatic enzyme capsules.

Adolescent↗
PubMed1993

Resting energy expenditure and substrate oxidation rates in cystic fibrosis.

The resting energy expenditure (REE) and substrate oxidation rates in 16 patients with cystic fibrosis who had mild chest disease and 11 healthy controls were measured using indirect calorimetry. The mean REE (% predicted) in the patients with cystic fibrosis was 11% greater than in the controls. Five patients with cystic fibrosis were hypermetabolic but only one of these had a clinically significant reduction of respiratory function. A greater proportion of REE was derived from carbohydrate oxidation in the cystic fibrosis patients (43.5% v 29.9%). However, the 24 hour dietary intake of carbohydrate was greater in the cystic fibrosis group (49.6 v 45.8% of energy intake). These data suggest that a high dietary intake of carbohydrate may contribute to the increased oxidation of carbohydrate in these cystic fibrosis patients. All patients with cystic fibrosis, including those with apparently mild lung disease, should continue to receive a high energy diet.

Adolescent↗