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Biomedical subjects

S Nicholls

Publications and source records attributed to S Nicholls.

At least 37 records · Page 2Linked to original sources
PubMed1994

The distribution of small bowel Crohn's disease in children compared to adults.

Barium follow-through (BaFT) examinations in 67 children and 114 adults with proven Crohn's disease (CD) were reviewed. Forty-six (68.7%) children and 62 (54.4%) adults had evidence of small bowel CD on BaFT. The frequency of CD in the proximal, mid and distal small bowel was 30.4%, 45.7% and 80.4%, respectively for children and 14.5%, 59.7% and 93.5% for adults. Children had significantly more duodenal/jejunal disease than adults (chi 2 = 3.99, P < 0.05) and significantly less terminal ileal disease (chi 2 = 4.29, P < 0.05). There was no significant difference in mid ileal disease. Nine (19.6%) children had small bowel CD with a normal terminal ileum compared with four (6.5%) adults. Ileoscopy-negative children have more proximal small bowel CD than adults and less distal disease. BaFT examination is essential if small bowel CD is not to be missed in children.

Adolescent↗
PubMed1994

Endoscopic features of chronic inflammatory bowel disease in childhood.

Flexible endoscopy, performed after oral bowel preparation and under moderate intravenous sedation, proves to be well tolerated, safe and highly effective in the diagnosis and management of children with IBD. At St Bartholomew's Hospital it is performed as the investigation of first choice, on the basis that it supplies colour documentation, histopathological and (where relevant) bacteriological evidence, which achieves certain confirmation or exclusion in almost every case and in the shortest possible time. Biopsies must always be taken, as mucosa of normal appearance can show either microscopic ulcerative colitis or Crohn's disease. When there are the characteristic 'aphthoid' ulcers, visual diagnosis of Crohn's disease is reasonably certain, particularly in early-stage disease, although amoebic and other infective causes of colitis can give misleadingly similar appearances. The endoscopist can usually inspect (and almost always biopsy) the terminal ileum, and can expect many children to show the prominent 'nodular lymphoid hyperplasia' which is essentially a normal finding-though sometimes misdiagnosed radiologically as being Crohn's deformity. However, it is important that radiological assessment by barium follow-through complements colonoscopy in view of the not infrequent cases of intestinal Crohn's disease in children where the proximal small intestine is involved, even if the colon and terminal ileum are spared.

Child↗
PubMed1994

Cyclosporin as initial treatment for Crohn's disease.

Childhood Crohn's disease may cause significant morbidity. T cell activation is considered to be central to Crohn's disease pathology, and as cyclosporin is a powerful inhibitor of T cell activation, and has been used in adult Crohn's disease with encouraging results, it may offer the prospect of remission if given early in the course of disease. Children with newly diagnosed Crohn's disease or those relapsing off treatment were therefore given cyclosporin or conventional treatment (enteral nutrition or corticosteroids) by random allocation. Evaluation was performed initially and at two months. Twenty four children were studied (10 on cyclosporin and 14 on conventional treatment; one child on cyclosporin withdrew). Significant clinical improvement occurred in the group on conventional treatment, but not in the cyclosporin group. Colonoscopic improvement was noted in 5/9 on cyclosporin and 8/14 on conventional treatment, but neither group produced a significant fall in median colonoscopic index. Histological improvement was seen in 7/8 on cyclosporin and 8/13 on conventional treatment, but cyclosporin was not significantly better. Cyclosporin produced improved clinical and histological appearance without matched improvement in blood disease indices. It was not better than conventional treatment, and simple oral administration is probably not suitable for newly diagnosed patients with Crohn's disease.

Adolescent↗
PubMed1993

Typing of Listeria spp. by random amplified polymorphic DNA (RAPD) analysis.

Random amplified polymorphic DNA (RAPD) analysis, a variation of the polymerase chain reaction (PCR) in which a single primer is used, was evaluated for use as a simple and reliable method with which to type Listeria spp. Representatives of six species of Listeria were studied. Five isolates of L. innocua and four isolates of L. seeligeri were all distinguishable from one another, but the four isolates of L. ivanovii tested, although distinguishable from other Listeria spp., were not differentiated. Among L. monocytogenes serovars 1/2a (eight isolates), 1/2b (eight isolates) and 4b (10 isolates), at least six, three and six RAPD patterns were observed, respectively. Fourteen neonatal cross-infection sets of L. monocytogenes isolates, shown to be indistinguishable by serotyping and phage typing, were examined with three different primers. With one primer, three of the sets were shown to consist of closely related, but distinguishable, strains. In the other 11 cases, each set of strains was indistinguishable with all three primers. These preliminary data indicate that RAPD analysis has promise as a method for typing Listeria spp.

Amino Acid Sequence↗
PubMed1993

Cytokines in stools of children with inflammatory bowel disease or infective diarrhoea.

AIMS: To determine the concentrations of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha) in stools from children. METHODS: Stool samples from 14 healthy children, 32 children with inflammatory bowel disease, and 23 children with acute diarrhoea were emulsified in an equal volume of phosphate buffered saline and then centrifuged to produce a clear supernatant fluid. IL-6 and TNF alpha were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: TNF alpha was detected in the stools of all 14 healthy children (12-130 pg/g stool), but IL-6 was detected only in three. Similar results were seen in children with inactive inflammatory bowel disease. Stool TNF alpha concentrations were raised in samples from children with active inflammatory bowel disease, but in most (11/18) of these samples IL-6 was undetectable. Stool samples contained a heat-labile factor which rapidly destroyed IL-6 immunoreactivity. Most children with diarrhoea had TNF alpha concentrations similar to those of healthy controls and most were also negative for IL-6. Three children with Shigella flexneri infection had extraordinarily high concentrations of both TNF alpha and IL-6 in their stools. CONCLUSIONS: There is constant low grade production of TNF alpha in the intestine of healthy people. Raised values are indicative of mucosal inflammation, but are not specific. Stool IL-6 is of little use in assessing mucosal inflammation because immunoreactivity is rapidly lost in stool samples.

Adolescent↗
PubMed1993

Cell proliferation in human arteriovenous fistulas used for hemodialysis.

The long-term patency of arteriovenous (AV) fistulas created for hemodialysis of renal-failure patients is usually measured in months, particularly when polytetrafluoroethylene (PTFE) material is interposed between the artery and vein. This is due to the rapid development of intimal hyperplastic lesions in the anastomosis region of the PTFE graft material with the vein. We studied the proliferative patterns in seven human AV fistulas removed at the time of fistula revision. Cell proliferation was determined by using an antibody to the proliferating cell nuclear antigen (PCNA), and specific cell types were identified by immunochemical reagents for smooth muscle cells, monocytes/macrophages, monocytes, lymphocytes, and endothelial cells. All venous segments exhibited a markedly hyperplastic intima. Vascularization of the intima and media by capillary-sized vessels was found. The main intimal cellular component was smooth muscle. Macrophages were usually seen around microvessels, and many also populated the perigraft region of the adventitia. In contrast to human atherosclerotic lesions, high rates of cell proliferation were observed in these fistulas. PCNA indices (percentage of cells that were PCNA positive [mean +/- SD]) were as follows: intima 17.7 +/- 11.3%, media 24 +/- 11.2%, and adventitia 20 +/- 11.6%. However, the distribution of PCNA-positive cells was not uniform. Instead, the PCNA index in microvessel-containing intimal fields was five to six times that of avascular fields (28.9 +/- 10.6% versus 4.9 +/- 4.5%, respectively, p < 0.001). Double immunolabeling revealed a large proportion of PCNA-positive microvascular endothelial cells and surrounding pericyte-like smooth muscle cells, as well as smooth muscle cells without visual connection to either microvessels or the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Stem cell factor directly stimulates the development of enriched granulocyte-macrophage colony-forming cells and promotes the effects of other colony-stimulating factors.

The effects of the c-kit ligand (stem cell factor [SCF]) on the development of a highly enriched population of granulocyte-macrophage colony-forming cells (GM-CFC) were assessed. In soft agar assays, both in serum-containing and in serum-deprived cultures, SCF promoted the formation of colonies that contained predominantly granulocytic cells with some blast cells also present. The size of these colonies was far smaller than observed in the presence of interleukin-3 (IL-3). In serum-deprived conditions, no colonies were formed in the presence of macrophage colony-stimulating factor (M-CSF), but when M-CSF was combined with SCF, a marked change was noted in that large colonies were produced containing predominantly macrophages. When GM-CFC were cultured in the presence of IL-3 and SCF, colonies were formed that contained blast cells, granulocytes, and macrophages. A synergistic interaction was also seen using a combination of G-CSF plus SCF in either serum-containing or serum-deprived cultures. The addition of SCF to colony-forming assays markedly reduced the concentration of IL-3 or G-CSF required for optimal levels of colony formation. Furthermore, SCF was capable of promoting the survival of GM-CFC for several days, after which large colonies containing mature cells were formed upon the addition of a secondary growth factor such as G-CSF or IL-3. Thus, SCF can directly act on highly enriched committed progenitor cells in serum-deprived conditions to promote survival, proliferation, and development.

Animals↗
PubMed1992

Tumour necrosis factor alpha in stool as a marker of intestinal inflammation.

Measurement of disease activity in patients with inflammatory bowel disease is difficult. The best available methods are complex and time consuming, but it may be possible to use tumour necrosis factor alpha (TNF alpha) concentration in stool as a marker of disease activity. We measured TNF alpha concentrations in stool samples from normal children, infants with diarrhoea, and children with inflammatory bowel disease in active and inactive phases of the disease. In 10 normal children and 14 children with diarrhoea, median stool TNF alpha concentrations were 58 and 45 pg/g stool, respectively. Compared with diarrhoeal controls, stool TNF alpha concentrations were significantly increased in children with active Crohn's disease (n = 13, median 994 pg/g, p less than 0.0002) and active ulcerative colitis (n = 4, range 276-5982 pg/g, p less than 0.003). In patients with inactive disease, either as a result of surgery or treatment with steroids, the concentration of stool TNF alpha fell to those of controls. Measurement of stool TNF alpha concentrations may provide a simple way to monitor disease activity in inflammatory bowel disease.

Adolescent↗
PubMed1980

A technique for studying the structural detail of isolated human corneocytes.

A technique for the isolation of human stratum corneum cells from any depth within the horny layer is described. Examination of the cells by light, scanning and transmission electron microscope permits a detailed morphological profile of the plasma membrane to be constructed. It is suggested that the technique will be of particular value in determining the effect of chemical agents on the cellular components of the horny layer.

Cell Membrane↗
PubMed1980

The 'dry' non-eczematous skin associated with atopic eczema.

The non-eczematous but 'dry' skin of twelve patients with eczema has been studied and contrasted with skin from similar sites in control subjects of similar age and sex and with patients with autosomal dominant ichthyosis. The areas investigated were examined histologically and by techniques for assessment of the stratum corneum structure and function. The 'dry' skin sites demonstrated increased intracorneal cohesion, increased total epidermal thickness, patchy parakeratosis and in places slight hypergranulosis. It is concluded that the dry skin condition of patients with atopic eczema is not autosomal dominant ichthyosis and is probably eczematous in nature.

Adolescent↗
PubMed1979

The change in properties of the stratum corneum as a function of depth.

The constancy of stratum corneum thickness suggests an ordered decrease in intracorneal cohesion binding forces. In this study, intracorneal cohesion was measured in the vertical dimension by cohesography and the number of cells released after applying a standardized stimulus was determined before and after repeated stripping of the same sites with adhesive tape. In addition, surface replicas and the corneocytes from different levels were examined by scanning and transmission electron microscopy and differential phase interference microscopy. The results indicate a gradual loss of cohesion within the stratum corneum towards the surface and that anatomical changes take place in the corneocytes as they progress towards the surface.

Adult↗
PubMed1979

Is the stratum corneum of uninvolved psoriatic skin abnormal?

A variety of abnormalities of the uninvolved skin have been reported in psoriasis, but there are few studies in which abnormalities of the stratum corneum (SC) have been investigated. In this study we have examined the intracorneal cohesion and structural detail of corneocytes of the SC from involved and uninvolved sites in 24 patients with psoriasis and 10 controls. We have found that intracorneal cohesion is increased in the involved and uninvolved skin of psoriatic patients compared to controls and that there are abnormalities of stratum corneum and corneocyte structure as determined by scanning electron microscopy. The changes in the uninvolved sites may well be due to the increased rate of epidermal cell production in these areas.

Adult↗
PubMed1978

Preliminary studies into percorneal penetration and elemental content of the stratum corneum using X-ray microanalysis.

A technique is described which measures the penetration of substances through the stratum corneum (SC) and the distribution of elements in this structure employing scanning electron microscopy and energy dispersive analysis. Preliminary observations show that the normal SC shows a concentration gradient of potassium, high in the surface layers and lowest deeper down whereas the reverse is true for phosphorus. It has been shown that sulphur rapidly tranverses the SC and seems to penetrate through all parts of the horny layer whereas lead and zinc do not easily enter this structure.

Adult↗
PubMed1977

Measurement of intracorneal cohesion in man using in vivo techniques.

Measurement of intracorneal cohesion in vivo should provide quantitative information concerning the process of esquamation. In this investigation three techniques have been employed to measure the internal binding forces within the stratum corneum in vivo. The first technique, cohesography, directly measures the force required to remove stratum corneum of partial thickness from a known area of skin. Sex and site differences were detected using this method. A second technique employs a surfometer to measure the surface contours of the internal face of skin surface biopsies. Quantitative assessment of surfometer tracings reflects both internal structure of stratum corneum and its cohesive property. Positive correlations were found using these two techniques on the forearms of 16 normal subjects. A scrub technique has also been used which can deliver a controllable and measurable stimulus to the skin surface to release corneocytes. Counting the number of corneocytes released provides a further measure of internal cohesion of the stratum corneum but the results did not correlate with the other two techniques. It is suggested that the use of all three techniques might provide a profile of the cohesive property of the stratum corneum.

Adolescent↗
PubMed1977

Novel techniques for the estimation of intracorneal cohesion in vivo.

Desquamation is the result of loss of cohesion between horny squames. This study is concerned with the in vivo measurement of intracorneal cohesion using three new techniques. A new instrument, the cohesograph, directly measures the force (g) required to distract a known area of partial thickness of stratum corneum in vivo. Sex and site differences were detected with this method. A surfometer was employed to measure the surface contours of the internal face of skin surface biopsies and when this measurement of the surface irregularity was compared to the 'cohesograph' reading for the same sites in 16 normal individuals a significant positive correlation of r=0-79 was found between the two sets of results. It is therefore suggested that the surfometer provides indirect measure of horny layer cohesion. Desquamation has also been estimated by using a modified 'scrub technique'. The scrub apparatus used is able to deliver a controlled stimulus to the skin surface to release horny cells. The light absorbance at 400 nm of corneocyte suspensions was measured and found to correlate well (r=0-96) with the numbers of squames released. It is suggested that the three techniques used in conjunction provide a profile of stratum corneum cohesion in vivo.

Adult↗