Search PubMed⌕ Search

Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 19 recordsLinked to original sources
PubMed2001

Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer.

We have identified 14-3-3 sigma (sigma) as a gene whose expression is lost in breast carcinomas, primarily by methylation-mediated silencing. In this report, we investigated the timing of loss of sigma gene expression during breast tumorigenesis in vivo. We analysed the methylation status of sigma in breast cancer precursor lesions using microdissection for selective tissue sampling. We found hypermethylation of sigma in 24 of 25 carcinomas (96%), 15 of 18 (83%) of ductal carcinoma in situ, and three of eight (38%) of atypical hyperplasias. None of the five hyperplasias without atypia showed sigma-hypermethylation. Unexpectedly, patients with breast cancer showed sigma hypermethylation in adjacent histologically normal breast epithelium, while this was never observed in individuals without evidence of breast cancer. Also, samples of periductal stromal breast tissue were consistently hypermethylated, underscoring the importance of selective tissue sampling for accurate assessment of 14-3-3-sigma methylation in breast epithelium. These results suggest that hypermethylation of 14-3-3-sigma occurs at an early stage in the progression to invasive breast cancer, and may occur in apparently normal epithelium adjacent to breast cancer. These results provide evidence that loss of expression of sigma is an early event in neoplastic transformation.

14-3-3 Proteins↗
PubMed2001

Partial nucleotide sequences, and routine typing by polymerase chain reaction-restriction fragment length polymorphism, of the brown trout (Salmo trutta) lactate dehydrogenase, LDH-C1*90 and *100 alleles.

The cDNA nucleotide sequences of the lactate dehydrogenase alleles LDH-C1*90 and *100 of brown trout (Salmo trutta) were found to differ at position 308 where an A is present in the *100 allele but a G is present in the *90 allele. This base substitution results in an amino acid change from aspartic acid at position 82 in the LDH-C1 100 allozyme to a glycine in the 90 allozyme. Since aspartic acid has a net negative charge whilst glycine is uncharged, this is consistent with the electrophoretic observation that the LDH-C1 100 allozyme has a more anodal mobility relative to the LDH-C1 90 allozyme. Based on alignment of the cDNA sequence with the mouse genomic sequence, a local primer set was designed, incorporating the variable position, and was found to give very good amplification with brown trout genomic DNA. Sequencing of this fragment confirmed the difference in both homozygous and heterozygous individuals. Digestion of the polymerase chain reaction products with BslI, a restriction enzyme specific for the site difference, gave one, two and three fragments for the two homozygotes and the heterozygote, respectively, following electrophoretic separation. This provides a DNA-based means of routine screening of the highly informative LDH-C1* polymorphism in brown trout population genetic studies. Primer sets presented could be used to sequence cDNA of other LDH* genes of brown trout and other species.

Alleles↗
PubMed2001

The role of symptomatic colds in asthma exacerbations: Influence of outdoor allergens and air pollutants.

BACKGROUND: Both air pollutants and respiratory viral infections have been recognized to be important triggers of asthma exacerbations, but the possible interaction of these has not been assessed in an epidemiologic study. OBJECTIVE: In this study, we aimed to assess the possible associations of symptomatic colds with outdoor allergens and air pollutants in exacerbating asthma. METHODS: A total of 57 adults and children with asthma participated in a 1-year study in Vancouver, British Columbia. Diary cards recording symptoms of asthma and colds, medication usage, and peak expiratory flow rates were completed twice daily. Outdoor air pollutant levels and levels of pollen and fungal spores were measured. Levels were examined for associations with exacerbations of asthma with symptoms of a cold, as compared with asthma exacerbations with no cold symptoms and colds in the absence of asthma exacerbations. RESULTS: Of 130 asthma exacerbations, 47% were associated with cold symptoms (accounting for 44% of episodes of colds). Asthma exacerbations with colds were associated with higher levels of sulfur dioxide, and nitric oxide during March to November in comparison with asthma exacerbations without cold symptoms (P <.018). Cold-symptom days overall were more common in winter and were significantly associated with lower temperatures, lower ozone levels, and higher sulfur dioxide, nitrogen dioxide, nitrogen oxide (NO and NO(x)), and carbon monoxide levels. CONCLUSIONS: Asthma exacerbations are commonly associated with cold symptoms. These episodes are associated with higher levels of sulfur dioxide and nitrogen oxides from March to November in comparison with asthma exacerbations without cold symptoms.

Adolescent↗
PubMed2001

Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease.

BACKGROUND AND AIMS: New lesions of Crohn's disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn's disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery. METHODS: Patients with Crohn's disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 microg/kg once daily (QD) (n=22) or 8 microg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment. RESULTS: Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%). CONCLUSION: Tenovil treatment for 12 consecutive weeks in patients with Crohn's disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn's disease by Tenovil was observed.

Adult↗
PubMed2001

The news on health care funding: a study of reporting in the Australian print media for 1996.

OBJECTIVES: To review the coverage of health care funding and resourcing issues in the quality printed media in Australia. METHODS: Content analysis of all articles in six major print publications with detailed commentary on four major issues. RESULTS: One thousand one hundred and fifty articles were published over 12 months, most in the front three pages. Coverage of many issues was prompted by an event, such as an election, government budget or policy announcement. Although issues were rarely personalized, the use of an individual authoritative spokesperson was, with some individuals becoming well recognised as experts. In general, these experts represented vested interest or lobby groups. The media discussion rarely dealt with the system as a whole, and generally approached a topic or issue in isolation from its inter-relationships with other issues. CONCLUSION: Health care funding stories are newsworthy but more for their political interest than as reflection of a social debate about values. Media reports rarely deal with the complexity of health policy issues, or challenge the assumptions and positions put forward.

Australia↗
PubMed2000

Ulcerative colitis.

Explore the source record for details and available documents.

Cholangitis, Sclerosing↗
PubMed2000

A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants.

BACKGROUND: The prevalence of asthma has increased in developed countries in the past 2 decades. The effectiveness of intervention measures on the primary prevention of asthma has not been well studied. OBJECTIVE: To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants (in this study, infants are defined as persons from birth to the age of 1 year). DESIGN: Prospective, prenatally randomized, controlled study with follow-up through the age of 1 year. SETTING: University hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and Winnipeg, Manitoba. PARTICIPANTS: A total of 545 high-risk infants (at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases) identified before birth. INTERVENTIONS: Avoidance of house dust mite and pet allergens and environmental tobacco smoke, encouragement of breastfeeding, and supplementation with a partially hydrolyzed formula. MAIN OUTCOME MEASURES: Probable or possible asthma, rhinitis without apparent colds, and a prick skin test result positive for common inhalant allergens. RESULTS: Thirty-eight (15.1%) of the 251 infants available for assessment in the intervention group and 49 (20.2%) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7% of the infants in the intervention group and 27.3% of the infants in the control group developed rhinitis without colds (adjusted relative risk, 0.51; 90% confidence interval, 0.35-0.74). The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups (4.4% in the intervention group and 4.6% in the control group). CONCLUSIONS: Our multifaceted intervention program resulted in a modest but significant (P= .04) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants. In the absence of a validated definition of asthma at the age of 12 months, follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants.

Asthma↗
PubMed2000

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months.

BACKGROUND: The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE: The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS: The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS: Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION: Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

Adult↗
PubMed2000

High intraluminal fluid flow increases intestinal IgA output.

BACKGROUND: Stool IgA output in normal stool or chronic diarrhoea is a fraction of that recorded in high-output watery diarrhoea due to cholera. We hypothesized that high intestinal fluid flow leads to increased IgA output, and this is not a consequence of reduced degradation/reabsorption. METHODS: Daily intestinal outputs of IgA and other secretory and non-secretory proteins were measured in stool from 14 volunteers with ileostomies and compared with the output during whole-gut lavage, a whole-gut perfusion system. RESULTS: Output into whole-gut lavage was significantly higher for all the proteins (P=0.02 to 0.001). Median IgA output into ileostomy effluent (IE) was 3.6 mg/kg/day compared with 26 mg/kg/day into whole-gut lavage fluid (WGLF). Thus IgA recovery in stool was only 12.7% of the amount in corresponding WGLF. Similar results were found for other proteins: specific IgA and IgM antibodies (5.4%-20.3%), IgM (42.4%), IgG (8.9%), and albumin (9.3%). Six subjects with IE water content >92% had increased recovery of IgA compared with eight with <92% water. In vitro, experiments predict that degradation of IgA within the small bowel results in 80% remaining compared with the 12.7% measured in vivo. CONCLUSIONS: Our data show that high intraluminal fluid flow increases the intestinal output of IgA and other proteins, and this is not a consequence of reduced degradation/reabsorption in the colon or small bowel. This increased protein output may be a non-specific response in the early stages of acute diarrhoea.

Adolescent↗
PubMed2000

Short-acting general anaesthesia facilitates therapeutic ERCP in frail elderly patients with benign extra-hepatic biliary disease.

AIMS AND OBJECTIVES: To ascertain whether therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for benign biliary disease in frail elderly patients with comorbid conditions can be safely undertaken in a district general hospital, and whether the procedure is facilitated by the use of short-acting general anaesthesia. SETTING: District general hospital in South East England. DESIGN OF STUDY: Clinical study of 25 consecutive patients with benign biliary disease. METHODS: Describes the process of bile duct clearance by therapeutic ERCP under short-acting general anaesthesia in 25 patients with co-morbidity aged > or = 80 years and gives details of the general anaesthesia and monitoring. RESULTS: Twenty-two patients had their bile ducts successfully cleared locally and one patient was stented for a benign biliary stricture. The ampullae of two other patients were lying within diverticula, which hindered cannulation and only pancreatograms were obtained; one of the patients had a successful bile duct clearance at a tertiary centre, the other refused further intervention. Complications (melaena, bronchopneumonia and a Clostridium difficile infection) occurred in two patients (8%). There was no morbidity associated with the anaesthesia, and no mortality occurred within 30 days of the procedure. CONCLUSIONS: Bile duct clearance by therapeutic ERCP can be safely carried out in frail elderly patients in a district general hospital and the process is facilitated by the use of short-acting general anaesthesia. The importance of optimizing the patient's condition before ERCP, and not overfilling the pancreatic duct, is highlighted.

Aged↗
PubMed2000

Intestinal inflammation in cystic fibrosis.

BACKGROUND: There is controversy about whether the inflammatory response observed in the cystic fibrosis (CF) lung occurs secondary to bacterial infection or is caused by a dysregulation of the inflammatory response associated with the basic cellular defect of CF. AIMS: To study the inflammatory response in the gastrointestinal tract of children with CF; and to investigate whether there is increased inflammation in the gastrointestinal tract of CF children with fibrosing colonopathy. METHODS: Whole gut lavage was performed on 21 pancreatic insufficient children with CF, who were clinically well, five children with CF and fibrosing colonopathy, and 12 controls. Intestinal outputs of plasma derived proteins (albumin, alpha(1) antitrypsin, IgG), secretory immunoglobulins (IgA and IgM), cellular constituents (eosinophil cationic protein and neutrophil elastase), and cytokines (interleukin 8 and interleukin 1beta) were measured. RESULTS: Compared to controls, the 21 CF patients, with no intestinal complications, had increased intestinal outputs of albumin, IgG, IgM, eosinophil cationic protein, neutrophil elastase, interleukin 1beta, and interleukin 8. Similar values were obtained for the CF patients with fibrosing colonopathy. CONCLUSIONS: These data suggest that there is immune activation in the gastrointestinal mucosa of children with cystic fibrosis, which may result from the basic cellular defect. Fibrosing colonopathy does not appear to be associated with increased inflammation.

Adolescent↗
PubMed1999

Umbilical cord blood mononuclear cell proliferative response to house dust mite does not predict the development of allergic rhinitis and asthma.

BACKGROUND: Cord blood mononuclear cells (CBMNCs) have been found to proliferate when stimulated with food or inhalant allergens. The significance of this finding is not known. OBJECTIVES: We sought to determine the factors associated with proliferation of CBMNCs when stimulated with house dust mite (HDM) allergen and to determine whether proliferation of CBMNCs is associated with subsequent development of HDM sensitization and development of allergic rhinitis and asthma. METHODS: Cord blood was taken from infants at high risk for having asthma and allergic diseases who were recruited for a primary prevention study in which infants were randomized into the intervention or the control group. CBMNCs were stimulated with HDM allergen and PHA as a positive control. Infants were assessed at 12 and 24 months for health outcome. RESULTS: When stimulated with HDM allergen, 29.7% of infants had a stimulation index (SI) of 2 or greater. There were no differences in the levels of cord blood IgE and cotinine, maternal smoking, immediate skin test reactivity, maternal IgE, and maternal exposure to HDM allergen between those with an SI of 2 or greater and those with an SI of less than 2. Infants with an SI of less than 2 had a significantly higher proportion of mothers with a history of asthma. No differences in the incidence of "asthma" and rhinitis without cold at 12 months and cumulative prevalence at 24 months were seen between the 2 groups. None of the infants had skin test reactions to HDM allergen. CONCLUSION: The negative association between HDM allergen-induced proliferation of CBMNCs and maternal mite allergen exposure and health outcomes at 12 and 24 months raises the issue of the significance of CBMNC proliferation.

Allergens↗
PubMed1999

Vaporisers.

Explore the source record for details and available documents.

Anesthesia, Inhalation↗
PubMed1999

The spectrum of ischaemic colitis.

OBJECTIVE: Ischaemic colitis is generally considered a disease of the elderly with considerable cardiovascular morbidity. We aimed to determine the effect of age, co-morbidity and clinical presentation on type, severity and anatomy of involvement of ischaemic colitis. Thrombophilic tendencies have been poorly studied and coagulation status was performed in available patients. DESIGN: Retrospective case identification with prospective follow-up. SETTING: University teaching hospital. PARTICIPANTS: Twenty-four patients (16 female, mean age 64 years) with ischaemic colitis. INTERVENTIONS: Blood analysis for clotting tendencies. MAIN OUTCOME MEASURES: Operation rates, death rates and frequency of clotting abnormalities. RESULTS: Five patients (21%) were below the age of 45, and seven of the 24 had died by the time of follow-up. Four had died of ischaemic colitis during the acute episode. The four patients that died of ischaemic colitis had a more extensive and more severe type of disease and presented with worse clinical features. The main predisposing factors were ischaemic heart disease in 12 (50%) and malignancy in five (21%). Six of the 24 cases (25%) had right-sided lesions and this conferred a good prognosis. Shock, peritonism, extensive disease and uncontrolled atrial fibrillation were all poor prognostic factors. Clotting factor abnormalities could be detected in three of nine patients despite a time lapse between assay and episode of ischaemic colitis. CONCLUSIONS: Ischaemic colitis appears to have two patterns of severity. Anatomical distribution is more variable than a developmental explanation of the vascular supply. Clotting abnormalities may be detected in a minority even on retrospective testing.

Acute Disease↗
PubMed1999

Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation.

BACKGROUND: Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing. AIMS: To compare the efficacy of PEG and lactulose in chronic constipation. METHODS: A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response. RESULTS: Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity. CONCLUSION: Low dose PEG 3350 was more effective than lactulose and better tolerated.

Adult↗
PubMed1999

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.

Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗