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Biomedical subjects

A D Phillips

Publications and source records attributed to A D Phillips.

At least 73 records · Page 4Linked to original sources

Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.

The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea.

Animals↗

Familial microvillous atrophy: a clinicopathological survey of 23 cases.

Twenty-three cases of microvillous atrophy were reviewed to determine clinical and morphological characteristics of the disease. Congenital and late-onset forms of presentation were clearly identified in which the late-onset cases appeared to have a better prognosis. Three different, and distinctive, appearances of the proximal small intestinal mucosa were found. Careful orientation of mucosal samples allowed a temporal sequence of events to be delineated in which the first morphological abnormality to be detected in the epithelium was the accumulation of "secretory granules"; microvillous inclusions were seen in older cells in the upper villous region. It is suggested that, in familial microvillous atrophy, diarrhoea and disorganisation of the brush border assembly occur as a consequence of a more fundamental defect that affects the intracellular traffic of certain cell components, as indicated by the accumulation of "secretory granules."

Aminopeptidases↗

Screening for enteropathogenic Escherichia coli in infants with diarrhea by the fluorescent-actin staining test.

The attaching effacing (AE) adherence property is now recognized as an important virulence characteristic of enteropathogenic Escherichia coli (EPEC). The fluorescent-actin staining (FAS) test (S. Knutton, T. Baldwin, P. H. Williams, and A. S. McNeish, Infect. Immun. 57:1290-1298, 1989), which is diagnostic for the AE lesions produced by EPEC (and Vero cytotoxin-producing E. coli), has provided an additional tool with which to investigate this important class of enteric pathogens. In this study, we screened for the AE adherence property in two groups of E. coli isolated from infants with diarrhea by using the FAS test and compared the results with those from O:H serotyping, localized adhesion to HEp-2 cells (LA), and the EPEC adherence factor (EAF) probe. Only 16 of 41 (39%) E. coli strains previously diagnosed as EPEC by O antigen serogrouping were FAS test positive, and of these only 12 belonged to recognized EPEC O:H serotypes; 9 strains which did belong to EPEC O:H serotypes were FAS test negative. Of a second group of 297 untyped E. coli, 7 (2.3%) were FAS test positive, and of these only 2 belonged to EPEC serogroups; 5 belonged to serogroups not regarded as EPEC serogroups or were nontypeable. Of the 23 FAS-test-positive strains identified, 10 were EAF probe positive and showed good LA; 13 were EAF probe negative and showed a quantitatively distinctly poor LA. EAF-positive and EAF-negative strains, however, showed equally good adhesion to human small intestinal mucosa. None of the FAS-test-positive E. coli hybridized with probes for Vero toxins 1 or 2. We conclude that the FAS test is diagnostic not only for classical EPEC and Vero cytotoxin-producing E. coli but also for EPEC strains which are not currently being diagnosed because they belong to serotypes not generally regarded as EPEC serotypes.

Actins↗

Response to autoimmune enteropathy to cyclosporin A therapy.

Small bowel enteropathies that are associated with an autoimmune process are often resistant to treatment. Two children with autoimmune enteropathy were treated with cyclosporin A for eight months. Both improved, as assessed by growth, small intestinal mucosal morphology, and carbohydrate absorption. Cyclosporin A is useful in the treatment of autoimmune enteropathy. This report also suggests that T cell activation (which is suppressed by cyclosporin A) is important in the pathogenesis of this condition.

Autoimmune Diseases↗

Enteropathogenic Escherichia coli and life threatening chronic diarrhoea.

Enteropathogenic Escherichia coli (EPEC) infection is not generally thought to cause severe diarrhoea after the neonatal period. Patients admitted to Queen Elizabeth Hospital for Children over the three years (1984-7) with diarrhoea and EPEC infection were reviewed. Clinical details, features of small intestinal mucosa, and treatment were recorded in those who developed chronic diarrhoea with failure to thrive. Twenty six children with EPEC required hospital admission for diarrhoea and six of these (23%) developed chronic diarrhoea. In contrast only two (5%) of 42 with other serogroups of E coli (p less than 0.01) and 28 (4%) of 764 children without EPEC admitted with acute diarrhoea developed chronic symptoms (p less than 0.01). EPEC serogroups detected in the stool of the six children with chronic diarrhoea were 0128 in three, 0114 in two, and 0119 in one. The patients' clinical characteristics were: previous good health, no significant immunodeficiency, age 4-10 months, foreign travel (three of six), severe life threatening secretory diarrhoea from 0.5 to 1.5 1 per day (four of six), small intestinal enteropathy (five of six) three of whom showed mucosal adherent, non-invasive E coli of the same serotype as that in the stool, in association with microvillous loss and pedestal formation. All were treated with hypoallergenic feeds, two with parenteral nutrition, and three with parenteral antibiotics. All eventually recovered. EPEC infection is a common treatable cause of life threatening chronic diarrhoea in infancy.

Child↗

Pathogenesis of gut virus infection.

In summary, the pathogenesis of many gut virus infections remains uncertain. However, human and animal studies indicate that the majority of gut viruses infect villous enterocytes. Viruses appear to have different affinities for enterocytes at different sites on the villus. Infection of enterocytes leads to cell death, extrusion into the lumen, and villous atrophy when the rate of cell production in the crypts cannot keep pace with the rate of enterocyte loss. This results in a reduced surface area as well as impairment of digestive and absorptive functions. This may also result in a net secretory state. All these changes, along with others such as reduced enzymatic activity and reduced epithelial integrity, may contribute to the induction of an acute but transient malabsorptive diarrhoea which may persist until the digestive/absorptive functions of the enterocyte are restored. However, if colonic compensation is sufficient to handle the increased fluid load, diarrhoea may not be evident. The roles of villous ischaemia, altered countercurrent exchanger of altered immune responses still remain uncertain and require further investigation.

Adenoviridae Infections↗

Abnormal expression of dipeptidylpeptidase IV activity in enterocyte brush-border membranes of children suffering from coeliac disease.

Dipeptidylpeptidase IV (DPP IV) activity has been shown cytochemically to decrease significantly in enterocytes of children suffering from coeliac disease. This decrease is due to a halving of the time available for enterocytes to express DPP IV in their brush-border membranes during development. This effect is compared with previous results showing coeliac disease to inhibit disaccharidase activities selectively.

Alkaline Phosphatase↗

Evaluation of a casein and a whey hydrolysate for treatment of cow's-milk-sensitive enteropathy.

A casein and a whey hydrolysate were evaluated in the management of 18 children with cow's-milk-sensitive enteropathy. This diagnosis was based upon clinical features, an abnormal small intestinal mucosa, i.e. an enteropathy, and a clinical response to cow's milk elimination. Two infants refused to take the whey hydrolysate. The median weight gain was higher in children given whey hydrolysate (19.4 g/day) than the casein hydrolysate (9.8 g/day). All children responded to cow's milk elimination and most had a significant improvement in small intestinal morphology after a cow's-milk-free diet. There was some advantage for the whey hydrolysate on morphometric analysis of their small intestinal mucosal response.

Animals↗

Rise and fall of coeliac disease 1960-85.

A total of 192 children who presented with coeliac disease to Queen Elizabeth Hospital for Children from 1960-85 were reviewed in order to investigate the frequency and the age of presentation. There was a clear peak in the number of children presenting from 1971-5, and although the numbers declined subsequently they have remained at a level similar to numbers found before 1971. There was no difference in the mode of presentation but there was a definite increase in the age of presentation over the time period reviewed. Breast fed babies presented later than bottle fed babies (14 compared with 9 months) despite a similar age of gluten introduction. Similarly bottle fed babies and breast fed babies presented later after 1975 (10.5 compared with 7 months, and 18 compared with 9.5 months, respectively). Before 1975 the median age of gluten introduction was significantly less than that after 1975 (2 compared with 4 months) and the age of gluten introduction correlated with the age of presentation. It is concluded that breast feeding and the age of gluten introduction may influence the age of presentation of childhood coeliac disease but no clear reasons for the rise in incidence in the 1970s have been determined. It does not appear that the disease is declining, however, in recent years children have tended to present later in life.

Acute Disease↗

Cows' milk sensitive enteropathy in cystic fibrosis.

Proximal small intestinal mucosal biopsies were carried out in children with cystic fibrosis who had diarrhoea and failed to thrive in spite of adequate treatment, including pancreatic supplements. Histological examination of eight of the 17 biopsies taken over a period of 12 years showed evidence of enteropathy, and accounted for one in 13 (8%) children with cystic fibrosis under 3 years of age attending our clinic. Seven responded to a cows' milk free diet; the diarrhoea stopped and weight gain increased. One of these responded only when gluten was also excluded from his diet. The eighth child remained on a normal diet and his symptoms did not improve. The enteropathy had resolved in all five patients who had further biopsies taken while receiving treatment, and from 15 months to 3 years of age all the children tolerated a normal diet and continued to thrive. Cows' milk sensitive enteropathy is an important cause of failure to thrive in children with cystic fibrosis. Small intestinal biopsy is an important investigation in younger children who fail to thrive and have diarrhoea despite adequate treatment.

Animals↗

An electron microscopical investigation of faecal small round viruses.

A retrospective study of small round featureless viruses (SRVs) initially identified by negative-staining electron microscopy of stool samples was performed. A variety of technique, including immunoelectron microscopy and caesium chloride gradient centrifugation, was applied in an attempt to classify further these viruses. Over a four-year period, 64 SRV-positive samples were reported (1.8% of the stool samples sent for electron microscopy and 6.2% of the total number of positive samples), of which 53 were available for further study. A significant degree of misclassification was found. Viruses previously identified as SRVs were shown to be astrovirus (n = 14), calicivirus (n = 2), and "Norwalk-like" virus (n = 1). The majority of the 36 remaining samples were identified as parvovirus-like (n = 27) (75%), 14 of which were associated with the presence of adenovirus particles. Enteroviruses (n = 3) and hepatitis A virus (n = 1) were infrequently detected. The remaining viruses (n = 5) could not be adequately classified. Parvovirus may be the predominant SRV associated with acute diarrhoeal disease in childhood.

Adenoviruses, Human↗

Investigation of hospital-acquired rotavirus gastroenteritis using RNA electrophoresis.

Rotavirus is a common cause of diarrhoea both in the community and in the hospital. Because of this, it may be difficult to determine whether crossinfection has occurred in the hospital, an important finding as review of hygienic techniques and ward closure may be indicated. We therefore investigated the use of Polyacrylamide gel electrophoresis (PAGE) of the rotavirus RNA genome as a means of distinguishing between rotavirus strains in order to assess its role in the evaluation of apparent hospital-acquired rotavirus diarrhoea. Suspected examples of hospital-acquired rotavirus gastroenteritis were studied on an infectious diseases ward and a general infant ward. PAGE analysis demonstrated that crossinfection had not occurred on the infectious diseases ward, even though this was indicated clinically; a single source outbreak involving 11 patients was confirmed on the general infant ward, as all cases showed an identical rotavirus electropherotype. Following ward closure an endemic rotavirus electropherotype was detected, which affected 17 patients over a 3-month period. Electrophoresis of rotavirus RNA is a useful and practical technique in the analysis of hospital-acquired gastroenteritis and can indicate appropriate clinical action.

Cross Infection↗

Selective alteration of brush-border hydrolases in intestinal diseases in childhood.

1. Biochemical estimates of lactase, sucrase and maltase activities, carried out on intestinal biopsies appearing histologically normal, were compared with those obtained from children suffering from coeliac disease, cow's milk protein intolerance/postenteritis syndrome and the intractable diarrhoea syndrome of infancy. Lactase deficiency in these children was found to be more pronounced than sucrase or maltase deficiencies. 2. Quantitative cytochemical investigations showed characteristic disease-induced changes in the ability of enterocytes to express alpha- and beta-glucosidases, but not alkaline phosphatase activities, during migration along stunted villi. 3. Separate estimates of the time course describing hydrolase development in normal and coeliac tissue showed the initial rate of lactase appearance to be halved in coeliac patients, while that for alpha-glucosidases remained constant and that for alkaline phosphatase increased by a factor of four. Enteroblastic replacement of mature enterocytes cannot provide a general explanation for hydrolase deficiency in diseased intestine.

Adolescent↗

Travellers' diarrhoea among children returning to the United Kingdom from visits abroad.

Between January 1984 and March 1986, 10 children aged between 7 and 56 months were admitted to Queen Elizabeth Hospital for Children in London with chronic travellers' diarrhoea, after visiting the Indian subcontinent, France or Morocco. All the children were born in the United Kingdom and had been in good health before their journey abroad. On return to England most of these children were malnourished and two of them (twins) had a post-infective, tropical malabsorption-like syndrome. There was a high incidence of positive stool cultures and, on small intestinal biopsy, histological abnormalities were present in six. Children from the United Kingdom travelling abroad are at risk of developing severe travellers' diarrhoea, with serious consequences to their health and nutrition. There is a need for intensive parental education before travelling and this could be achieved through community health workers.

Bacterial Infections↗