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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

New polyethylene glycol electrolyte solution for the treatment of constipation and faecal impaction.

Results from a controlled clinical trial indicate that low doses of polyethylene glycol solutions are more effective and have fewer side-effects than lactulose. Large doses of polyethylene glycol are effective in the treatment of faecal impaction. Resolution of faecal impaction was obtained in all patients, and in 25/30 patients with three administrations in a three-day period.

Adolescent↗
PubMed1998

Heterogeneity of celiac disease: clinical, pathological, immunological, and genetic.

In this paper we consider recent new data on the pathological features of gluten sensitivity and on the disease-associated antigens, in the context of a multistage hypothesis that we have been developing for the last five years. This incorporates concepts of oral tolerance induction, mucosal T-cell and antibody-mediated injury, and genetic contributions. Until now, there has been complete agreement that the diagnosis of celiac disease must be based on small bowel histology. There are patients with low-grade gluten-sensitive enteropathy, in whom the only morphological abnormality is a high count of intraepithelial lymphocytes (IEL). Some, but not all, also have positive serum IgA anti-endomysium antibody (AEA). With good techniques, in a properly accredited laboratory, in a patient suspected on clinical grounds to have celiac disease, a positive serum IgA AEA test (perhaps, alternatively, high-titer anti-transglutaminase by ELISA), is virtually diagnostic of the condition. Our hypothesis of a stepwise pathogenesis of severe gluten-sensitive enteropathy is re-examined in the light of these new data. It is evident that there are at least five different levels at which genetic influences may operate.

Animals↗
PubMed1998

Autoantibodies to tissue transglutaminase as predictors of celiac disease.

BACKGROUND & AIMS: Immunoglobulin A (IgA) autoantibodies to endomysium (EMA) are highly specific and sensitive markers for celiac disease. Recently, we identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen. METHODS: An enzyme-linked immunosorbent assay (ELISA) was established to measure IgA anti-tTG titers in serum samples from 106 celiac patients with partial or subtotal villous atrophy, 43 celiac patients on a gluten-free diet, and 114 diseased and healthy controls. Results were correlated with clinical and histological data and with EMA titers. RESULTS: In patients with biopsy-proven celiac disease consuming a normal, gluten-containing diet, 98.1% of the serum samples had elevated IgA titers against tTG, whereas 94.7% of the control sera were negative. IgA anti-tTG correlated positively with semiquantitative IgA EMA titers (r = 0.862; P < 0.0001). CONCLUSIONS: An ELISA based on tTG allows diagnosis of celiac disease with a high sensitivity and specificity. IgA anti-tTG and IgA EMA show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen. Because the assay is quantitative, not subjected to interobserver variation, and easy to perform, it will be a useful tool for population screening of a hitherto underdiagnosed disease.

Adolescent↗
PubMed1998

Crohn's disease: nutrition and nutritional therapy.

Disordered nutrition is common in Crohn's disease and is multifactorial. Regular and systematic monitoring of at least a minimum set of nutrition data is an essential component of care of children and adults with Crohn's disease. However, even in children, monitoring of growth and development may be deficient. Multiple macro- and micronutrient deficiencies are common in Crohn's disease, especially in those with extensive small bowel deficiencies or after multiple surgical resections. Body composition analysis may show differences from simple starvation, and metabolic effects of inflammation are increasingly being recognized. Nutritional support is part of the management of all patients with Crohn's disease, but nutritional intervention with defined formula liquid diet is an effective specific anti-inflammatory therapy. Although meta-analysis of published trials suggest that steroids are more effective than defined formula liquid diets, objective evidence from whole gut lavage fluid analysis and from faecal excretion of radiolabelled leukocytes shows unequivocal benefit of elemental diet based on measuring parameters of tissue damage. Enteral feeding with liquid diets should be considered in patients with incomplete small bowel obstruction, severe painful perianal disease, failure of corticosteroids in active Crohn's disease, borderline intestinal failure and in children with active Crohn's disease or with growth failure.

Body Composition↗
PubMed1998

Discharge planning in A & E: part 2.

Discharge of patients from A & E was considered by both the 1992 and 1996 Audit Commission reports. The 1992 Commission recommended that unnecessary return attendance for follow-up care should be reduced to a minimum, those requiring to make a return visit falling within the range of 10-15% of first attendances. Other hospital specialties, GP services and self care were identified as appropriate follow-up treatment. This places more emphasis on appropriate discharge advice for those who do not need to reattend, and this is an aspect of health promotion which largely goes unrecognized. The second part of this study explores how effectively A & E departments perform the role of giving appropriate discharge advice. Part I of the study, published in October 1997, covered the comprehensive discharge planning required for patients who belong to vulnerable groups and who commonly reattend.

Aftercare↗