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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 55 records · Page 3Linked to original sources

Oral budesonide as maintenance therapy in Crohn's disease--results of a 12-month study. Global Budesonide Study Group.

BACKGROUND: Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease. METHODS: In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time. RESULTS: There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096). CONCLUSIONS: In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.

Adolescent↗

Regional implementation of a national cancer policy: taking forward multiprofessional, collaborative cancer care.

The vision of the Calman-Hine paper is of patient-centred care, delivered by co-ordinated services which have genuine partnerships with each other. There is integration of other providers of support, to meet psychological and non-clinical needs. There is access to palliative care when required, from diagnosis onwards, and not just in the terminal stage. Effective communications and networks are the keys to making this vision a reality. Our recommendations are based upon in-depth discussions with purchasers, doctors and nurses, and others involved with cancer services within hospitals or the community across the region. They reflect the priorities placed on the development of good practice. Purchasers and providers should work together to implement these guidelines.

Communication↗

Notification of tuberculosis in patients with AIDS.

BACKGROUND: In the early 1990s cases of tuberculosis in people with HIV infection and AIDS were undernotified. A study to evaluate changes in notification rates in two inner London local authorities was undertaken for the period January 1993-June 1996 inclusive. METHODS: For residents of the two local authorities, tuberculosis notifications were identified using a local database, and cases of AIDS with a recorded diagnosis of tuberculosis were identified from AIDS case reports. RESULTS: During the study period, only 13 (32 per cent) of the 41 AIDS cases with a recorded diagnosis of tuberculosis were also notified as a case of tuberculosis. However, the proportion of notified cases rose from 0 per cent (0 of 11) in 1993 to 50 per cent (5 of 10) in 1995 and 63 per cent (5 of 8) in early 1996. CONCLUSION: The increase in the tuberculosis notification rate for people with AIDS is encouraging, but scope for improvement remains.

AIDS-Related Opportunistic Infections↗

Absence of detectable measles virus genome sequence in inflammatory bowel disease tissues and peripheral blood lymphocytes.

A highly sensitive measles-specific RT-PCR-nested PCR system was established, which consistently amplified measles virus genome sequence from control samples containing as little as 5.5 x 10(-3) pfu per reaction. This method failed to detect the presence of measles virus in 93 colonoscopic biopsies and 31 peripheral blood lymphocyte preparations, examined and obtained from patients with inflammatory bowel disease (IBD) and noninflammatory controls. All patients had detectable levels of serum neutralization antibody against measles virus. Each biopsy was estimated to have about one million cells, based on the amplification of the beta actin gene. The assay was calibrated by use of a known number of lymphocytes. The method applied was able to amplify measles virus RNA from a nucleic acid mixture equivalent to 18 cells derived from subacute sclerosing panencephalitis (SSPE) brain material. The level of measles RNA present, if any, in the biopsies is therefore at least 50,000-fold less than in SSPE.

Adult↗

Highly effective new oral therapy for faecal impaction.

We reasoned that relief of faecal impaction could be achieved if a bolus of polyethylene glycol/electrolyte solution was delivered to the caecum over a few hours. Thus, 16 patients with faecal impaction (duration of constipation 5-23 days) were treated in an open study with up to three daily treatments of one litre of polyethylene glycol/electrolyte solution daily, taken orally over 4-6 hours. Complete resolution of impaction, strictly defined, was obtained in 13 patients, and significant improvement in the other three. Only one patient was faecally incontinent and the only side-effect was an increase in borborygmi. Polyethylene glycol/electrolyte solution, given as a treatment dose of one litre daily for up to three days, is a highly effective and acceptable oral therapy for faecal impaction.

Adult↗

Overexpression of ZBP-89, a zinc finger DNA binding protein, in gastric cancer.

ZBP-89 is a Krüppel-type zinc finger protein that binds to the gastrin EGF response element (gERE). Sp1 binds to the same DNA element and transactivates gastrin promoter activity, whereas ZBP-89 competes for Sp1 binding and prevents EGF induction. Both transcription factors mediate growth factor signals originating from the EGF receptor and thus were studied in normal and neoplastic tissues or cell lines. When compared to normal tissue from the same patient, ZBP-89 protein expression was increased in neoplastic tissue from the stomach antrum and in malignant cell lines. RT-PCR analysis of ZBP-89 mRNA correlated with protein overexpression. Immunocytochemical studies confirmed that ZBP-89 expression is elevated in neoplastic tissue and chronic gastritis, whereas Sp1 expression was nearly unchanged. These results suggest that the transcription factor ZBP-89, like Sp1, may be a marker for neoplastic transformation in some gastric cancers.

Cells, Cultured↗

Discharge planning from A & E: Part I.

The discharge of patients from hospital has always been a vital part of the nurse's role. The government recognized the need for health personnel to plan effective discharge of patients from hospital and guidelines were produced by the Department of Health in 1989. While these were aimed more at the inpatient than the Accident and Emergency (A & E) attender, many of the recommendations can be applied to the emergency setting. Nowhere more than A & E does this create a management problem for patients, carers and colleagues alike. Those patients that belong to vulnerable groups, the elderly, the homeless, children and the mentally ill require a comprehensive discharge programme, utilizing the skills and knowledge of a number of community care personnel. Current practices are explored and recommendations made for future management. Part 2 of the study, covering appropriate discharge advice for patients who do not need to reattend the department, will be published in 1998.

Adult↗

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Celiac Disease↗

Detection of insulin-like growth factor-I and transforming growth factor-beta in whole gut lavage fluid: a novel method of studying intestinal fibrosis.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and/or transforming growth factor-beta (IGF-beta), may be involved in gut fibrous strictures. METHODS: Concentrations of these two peptides have been measured by enzyme-linked immunosorbent assays (ELISAs) in whole gut lavage fluid from 57 patients, of whom 14 had strictures of the small intestine or colon associated with Crohn's disease, irradiation injury, ischaemia or diverticulitis. RESULTS: IGF-I was detected in fluid from 11 of 14 patients with strictures, and 5 of 43 others (P < 0.01). TGF-beta was detectable in all 57 samples and concentrations were unrelated to the presence or absence of strictures. CONCLUSION: Clinical studies of growth factors in intestinal fluid should facilitate research on intestinal fibrogenesis, and the diagnosis of fibrous stricturing in Crohn's disease.

Crohn Disease↗

Successful pregnancy in a patient with chronic intestinal pseudo-obstruction while on ambulatory percutaneous endoscopic gastrostomy feeding.

We report a case of ambulatory endoscopic gastrostomy feeding via a low profile button device using a portable feeding pump. This provided successful nutritional support to a patient with chronic intestinal pseudo-obstruction who became pregnant while on gastrostomy feeding. She successfully completed her pregnancy with nutritional support through the gastrostomy. The portable feeding pump gave her excellent quality of life both indoors and outdoors, and she could continue feeding without interrupting her daily housework, shopping and babycare.

Adult↗

Body composition at the bedside.

OBJECTIVE: To evaluate the use of an inexpensive hand-held bioelectric impedance analysis machine which measures lean body mass, by technical comparisons against standard instruments and techniques (an in-house bioelectric impedance machine and dual energy X-ray absorptiometry), and by performing body composition analyses in groups of potentially malnourished patients. DESIGN: Prospective simultaneous comparison of measurements made by the hand-held and in-house bioelectric analysis machines and dual energy x-ray absorptiometry. SETTING: Medical Physics Department and Gastrointestinal Unit in a university teaching hospital. SUBJECTS/METHODS: One hundred and sixty subjects were recruited into the study. Data from 58 adolescent and 14 adult volunteers and from 42 adult patients were used for technical comparisons (n = 114). Body composition information was evaluated (n = 102) for 60 adult volunteers and 42 patients (17 with eating disorders, 7 with chronic alcoholic pancreatitis and 18 with inflammatory bowel disease). OUTCOME MEASURES: Estimation of bias, limits of agreement and correlations on data from the three machines. Relationships between percentage body mass as lean, absolute weights and body mass index, in the adult subjects. RESULTS: Both resistance and calculated impedance measured by the hand-held machine significantly correlated with the impedance measured by the in-house machine (r = 0.996; P < 0.0001). An estimation of the level of agreement in percentage lean measurement between dual energy x-ray absorptiometry and hand-held bioelectrical impedance analysis machine by the Bland and Altman method showed a bias of -0.07% and satisfactory limits of agreement from -7.97% to 7.76%. Body mass index was similar in the groups of healthy men and women, but proportion of weight as lean was significantly higher in men than women. In underweight patients with eating disorders, the ratio of lean to fat varied widely; in inflammatory bowel disease patients, proportions of lean and fat were similar to controls; however patients with alcoholic pancreatitis had values for body mass index similar to controls, but had significantly lower proportion of their body weight as lean (P < 0.05). CONCLUSION: In non-obese and thin adults, an accurate two-compartment (lean, fat) measurement of body composition can be made in 10 min by using an inexpensive, hand-held, bioelectric impedance analysis machine.

Absorptiometry, Photon↗

Assessment and management of ulcerative colitis in children.

The incidence of ulcerative colitis in school-age children in most parts of Europe has been steady at 1.5-2.0 per 100,000 children per year for the last 20-30 years. In comparison to adults, abdominal pain is a relatively frequent presenting symptom in children in addition to rectal bleeding, bloody diarrhoea or diarrhoea. Distribution of disease in children is generally more extensive (ratio rectal:left sided:extensive 25:30:45). There are remarkably few clinical trials of therapy in children and reasons for this are discussed. Subjective indices of disease severity and activity are unreliable in children. Objective measures such as endoscopy are of value to define the extent of ulceration and histopathological features; a test of gut protein loss using whole gut lavage gives an objective index of disease activity. Principles of medical management in children are generally the same as in adults with the additional need for scrupulous attention to nutrition and growth, and psychological factors. Reassuring results of a review of the health status of young adults who had developed ulcerative colitis in childhood are presented. Twenty-four of 27 considered themselves fully fit although nine of the patients had a permanent ileostomy.

Adolescent↗

Mucosa-associated bacterial flora of the human colon.

Biopsy samples of mucosa were taken during colonoscopy from the proximal colon and rectum of 12 patients, six with ulcerative colitis (UC) and six with non-inflammatory conditions. After anaerobic transport to the laboratory, biopsy specimens were examined by quantitative bacteriological culture on selective and non-selective media for total aerobic count, total anaerobic count, Bacteroides spp., lactobacilli, bifidobacteria and asaccharolytic, lactic acid producers. Isolates of the genus Bacteroides were identified to species level. Counts from proximal colonic and rectal biopsy samples in the same patient were not significantly different. Viable aerobic counts (aerobes and facultative organisms) ranged from 2.4 x 10(3) to 1.3 x 10(6) cfu/sample biopsy (5.6 mg) and total anaerobic counts were 10-10(2) times higher at (1.4 x 10(5))-(3 x 10(7)) cfu/sample. Bacteroides spp. predominated at both sites (range 8.6 X 10(4) to 1.4 x 10(7) cfu/sample), comprising 66% of total counts from proximal colon (range in individual patients 31-80%) and 68.5% from rectum (range 38-91%). Lactobacilli were isolated from eight biopsy samples from five patients, counts ranging from 3.6 X 10(2) to 1 X 10(5) cfu/sample; bifidobacteria were isolated from both sites from 10 of the 12 patients, counts ranging from 50 to 1.8 x 10(6) cfu/sample. From the 24 biopsy samples, 235 isolates representing 11 species of Bacteroides were identified. For any individual patient, only a few species (2-7; mean 4.4) of Bacteroides were found, with just one or two species predominating. B. vulgatus was cultured from both samples of seven patients (where it was the major isolate in four) and from single samples of two others; B. fragilis was cultured from both sites in six patients, being the major isolate in one patient and second commonest in three, but was not detected in the other six; the majority of other isolates were B. merdae/distasonis, B. ovatus, B. thetaiotaomicron and B. uniformis. B. thetaiotaomicron was isolated from both biopsy samples in all three UC patients with active inflammation (16 of the 60 isolates from these patients) but from only four of the other 18 samples from non-inflamed colonic mucosa (nine of 175 isolates).

Adult↗

Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group.

BACKGROUND: The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism. AIMS: To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon. PATIENTS AND METHODS: One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less. RESULTS: After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023). CONCLUSIONS: Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.

Acute Disease↗