Biomedical subjects

K E Carr

Publications and source records attributed to K E Carr.

At least 19 recordsLinked to original sources

PubMed1996

The effect of graft-bed irradiation on the healing of rat skin grafts.

This study explores the possible side effects on healing skin grafts of irradiation, commonly used intraoperatively following surgical tumor removal. The experimental model involved the delivery of a single 10-Gy dose of electron radiation to the recipient bed of a skin wound, followed by attachment of a full thickness rat skin autograft. Skin graft repair was assessed by light microscopy, immunohistochemistry, and transmission electron microscopy over a 3-week period for grafted and grafted-irradiated groups. Graft-bed irradiation reduced fibrinogen, fibrin, and fibronectin deposition in the wound. It also produced brief changes in the extent of both re-epithelialization and granulation tissue formation, and reduced the diameter of collagen fibrils in the granulation tissue. Despite these changes, the results suggest that graft-bed irradiation only delays the healing process, producing no serious clinical complications at the time points studied.

Animals↗

PubMed1996

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone.

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

Animals↗

PubMed1996

Morphological profiles of neutron and X-irradiated small intestine.

This paper describes the response of mouse small intestine, at several time points after treatment with neutron or X-irradiation, using doses expected to give similar effects in terms of crypt/microcolony survival. Using resin histology, the effects of radiation on the numbers of duodenal cell types and measurements of tissue areas were assessed. The results for individual parameters and for an estimate of overall damage are given in a data display, which summarises the morphological profile of the organ after both types of radiation. Damage and recovery were seen for many of the parameters studied but there was no standard response pattern applicable for all parameters. In particular, the response of individual crypt cell types could not be predicted from knowledge of the change in crypt numbers. With regard to the holistic response of the gut, neutron irradiation appeared to have caused more damage and produced more early effects than the X-irradiation. More specifically, neutron treatment led to more damage to the neuromuscular components of the wall, while X-irradiation produced early vascular changes.

Animals↗

PubMed1996

The application of microridge analysis in the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: The percentage of epithelial surface area covered by microridges (%MR) seen during scanning electron microscopy of oesophageal biopsy specimens has previously been shown to correlate with symptomatic reflux disease, a result < or = 35% being abnormal. The aim of this study was to compare %MR with endoscopy, light microscopy, and pH monitoring results. METHODS: Sixty-seven patients with heartburn were divided into oesophagitis or none on the basis of endoscopy and light microscopy findings and into those with and without abnormal acid reflux on the basis of pH monitoring. RESULTS: The endoscopic and light microscopic oesophagitis groups had significantly greater degrees of acid reflux than those without oesophagitis (p < 0.05), even though neither the specific %MR nor the number of patients below the 35% cutoff showed any difference between those with and without endoscopic oesophagitis, light microscopic oesophagitis or those with normal and abnormal acid reflux on pH monitoring. CONCLUSION: Despite the significant relationship between endoscopic and light microscopic oesophagitis and abnormal pH monitoring microridge analysis did not correlate with any of these variables

Biopsy↗

PubMed1996

Ultrastructural observations on the peritoneum in the mouse.

The serous mesothelium of the serosa and mesentery of the small intestine in the mouse were examined by scanning and transmission electron microscopy. The serosa consisted of a single layer of flattened microvilli-bearing cells containing nuclei, caveolae and micropinocytotic vesicles. The observations in this study differed from previous reports on mesothelial surfaces in two respects. A surface layer of amorphous material was present over parts of the serosa. This layer probably represents serous fluid trapped by the mesothelial microvilli but is unaffected by prefixation rinsing in saline or ultrasonic cleaning. The layer is lost following osmication and routine processing for transmission electron microscopy. The possibility that a serous fluid layer may be preserved in this way may be useful in assessing changes in the peritoneum. Stomata were observed in the mesentery but there was no evidence of a connection with the lymphatic system. The presence of mesenteric stomata may explain the difference in permeability reported between parietal peritoneum and mesentery.

Animals↗

PubMed1996

Morphometric analysis of the small intestinal epithelium in the indomethacin-treated mouse.

To obtain a clearer understanding of the changes which are induced in the small intestine of the mouse by an ulcerogenic dose of indomethacin, a quantitative analysis of the nonulcerated small intestinal mucosa was performed in mice that were given 2 injections of indomethacin at a dose of 85 mg/kg body weight. At 20 h after the administration of the drug, values were obtained for epithelial volume, whole crypt number, and for the number of profiles of columnar, Paneth, entero-endocrine and goblet cells and cryptal mitotic figures in the small intestine. Comparison of the values obtained from indomethacin-treated mice with those from control mice showed that there were fewer whole crypts and a reduced epithelial volume in the jejunum and ileum in indomethacin-treated mice. The numbers of columnar and Paneth cell profiles and of mitotic figures were significantly greater in the jejunal and ileal crypts in indomethacin-treated mice than in controls. These findings suggest that the administration of high-dose indomethacin in the mouse leads to crypt losses and increased mitotic activity in the nonulcerated parts of the small intestine.

Animals↗

PubMed1995

Uptake and translocation of microparticles in small intestine. Morphology and quantification of particle distribution.

The intestinal transit of large (micro-) particles to other sites of the body remains a controversial issue of relevance in various fields of study. In this report fluorescent polystyrene latex microparticles in the size range of 2 microns were used as models for nonspecifically absorbed nonbiodegradable particulates. They were administered to young adult rats as a single oral dose of 1.65 x 10(9) particles; Peyer's patches and surrounding normal absorptive small intestinal tissue were collected at various time points. Quantification of solubilized tissue samples and fluorescence (epi- and confocal) qualitative and quantitative microscopy showed uptake of latex microparticles in all parts of the intestine sampled, but with the proximal segment the preferential site of absorption. The maximum uptake of particles occurred 0.5 hr after dosing in all three segments of the small intestine; there were progressively smaller numbers with distance from the pylorus and with time. Translocation of small numbers of particles to the mesenteric lymph nodes was also detected at 0.5 hr. Transmucosal passage of particles occurred primarily in the villous tissues adjacent to the Peyer's patch regions. These studies give confirmatory evidence for the uptake and translocation of microparticulates across the mucosal barrier and provide new information regarding site- and time-related effects on particle uptake and the involvement of the villous epithelium in particle translocation.

Animals↗

PubMed1995

A commentary on morphological and quantitative aspects of microparticle translocation across the gastrointestinal mucosa.

It is now generally accepted that particulates in the nano-range (< 1 micron) can and do cross the intestinal mucosa. However, the issue is less well resolved for particles in the micro-range (> 1 micron) and this is discussed in relation to the variety of experimental designs present in the literature. Emphasis is placed on the relative contributions of quantitative bulk tissue analysis with respect to qualitative and quantitative morphological analysis. The discussion is extended to observations on factors influencing the particle translocation process including variation in particle uptake in relation to intestinal region and time post-dose administration based on data for uptake of -2 microns latex particles by rat Peyer's patch tissue. Although a significant body of data now identifies the intestinal processus of particle translocation it is underlined that discrepancies may arise as a consequence of different analytical approaches and that this is an issue to be addressed for valid comparisons of data.

Animals↗

PubMed1995

Morphological aspects of particle translocation in vivo following ingestion of the yeast Saccharomyces boulardii.

Particle translocation in vivo was studied in mice using the non-pathogenic yeast Saccharomyces boulardii (SB). Seven day old BALB/c mice were given either saline (control) or 1.5 g/Kg SB (every six hours, up to 48 hours), by intubation, and killed by decapitation 48 hours post-treatment. Light and scanning electron microscopy (SEM) examination of specimens prepared from the middle intestine revealed the presence of yeast inclusions localised in the cytoplasm of enterocytes.

Animals↗

PubMed1995

A morphological and microanalytical investigation into the uptake of particulate iron across the gastrointestinal tract of rats.

The uptake and translocation of particulate iron across the gastrointestinal (GI) mucosa of young adult rats has been investigated using a range of morphological techniques and X-ray microanalysis (XRMA). In animals fed a suspension of iron powder constituted of metallic iron particles ranging in size from 6-9 microns down to 5-30 nm, light microscopic histochemistry has clearly revealed iron deposits within the tissues of the duodenum. Scanning electron microscopy of the duodenal tissue by back-scattered electron imaging has complemented the light microscopic observations and revealed a selective localization of iron in the villi with variation in levels of iron uptake by the mucosal cells. Ultrastructural and XRMA analysis of duodenum has established the presence of metallic iron nanoparticles within the brush border, lateral intercellular spaces of the mucosal cells, mitochondrial cristae and cytoplasm of both mucosal and stromal cells. The observations indicate that metallic iron particles, in the nano-size range, may be taken up by the GI mucosa and that the passage of such particles across the epithelial barrier may take place through both a paracellular as well as a transcytotic process.

Animals↗

PubMed1994

Electron irradiation slows down wound repair in rat skin: a morphological investigation.

To date, there have been few morphological investigations of the effect of electron radiation on the healing of skin wounds in rats. The present morphological study examines the wound repair process in electron-irradiated rat skin by electron microscopy. Standardized, full-thickness, incisional wounds were made in the lower dorsal skin of animals which had been locally irradiated with 9.6 Gy electron radiation 7 days previously. The irradiation dose was maximal at 3 mm depth. Twenty-four rats were used in the investigation; 12 were irradiated and 12 sham-irradiated. Three rats from each experimental group were killed at 1, 3, 7 and 14-day time intervals after wounding. The morphological effect of electron irradiation on the repair of each wound was investigated by light microscopy (LM) and scanning electron microscopy (SEM). New granulation tissue visualized by SEM was quantified using computerized image analysis. The results suggest that a single, partial-body, controlled depth dose of electron irradiation delays wound repair. LM showed that there is a depression of the inflammatory cell and tissue exudate response, slowing of epithelial migration, and a decrease in fibroblast representation, together with a delay in the formation of collagen bundles. Granulation tissue formation was impaired up to 7 days post-wounding, but was restored to around control values by day 14, indicating that healing was delayed. However, as the healing of normal tissue was not prevented, this study supports a preoperative role for the use of low-dose electron irradiation therapy for the treatment of electron-sensitive superficial pathologies in surgical practice.

Animals↗

PubMed1993

Structural and morphometric analysis of murine small intestine after indomethacin administration.

Indomethacin, a nonsteroidal anti-inflammatory drug, induces the formation of gastrointestinal ulceration both in experimental animals and in humans. A study of indomethacin-induced ulcers in the mouse showed that two doses of indomethacin, each administered subcutaneously at 85 mg/kg body weight, induced well-defined gastrointestinal ulcers in C57 mice, accompanied by inflammatory and vascular changes in the stomach and small intestine. Maximal damage was observed 20 h after the second dose of indomethacin. Morphometric analysis identified changes in all compartments of the small intestine. There was a marked reduction in the length of the small intestine, intestinal dilatation, a significant decrease in villous height, with the formation of subepithelial blisters or blebs within villi, and submucosal vascular dilatation. There was no change in the number of villi or of submucosal arterioles or in the total amount of muscle present in the wall of the intestine. The tissue changes identified in this study may have implications for gut function at specific periods during indomethacin treatment.

Animals↗

PubMed1993

Rabbit and human non-keratinising stratified squamous oesophageal epithelium displays similar microridge structure by scanning electron microscopy.

Since the oesophageal epithelium of common laboratory animals, rats and mice, is keratinized it is unsuitable for comparison with typical non-keratinized stratified squamous human epithelium. It is thus important to find a suitable animal model for the study of human oesophageal tissue changes. This study investigated the microridge structure of immature and adult rabbit specimens, and adult human biopsies by scanning electron microscopy and morphometry. The investigation revealed a similarity between typical squamous human and adult rabbit oesophageal mucosal epithelium. While human epithelium specimens subdivided into two other groups (non-typical squamous and non-squamous); all typical squamous human biopsies were from patients who had normal endoscopy reports and no reflux symptoms. The surface cells of typical squamous human epithelium displayed complex microridge patterns (64% of cell surface) but patterns in non-typical squamous specimens were more variable (38%) (P < 0.001) and cell boundaries less obvious. Rabbit squames displayed clear microridge patterns with an elevation in the percentage of cell surface covered by microridges, with increasing age, from immature to adult specimens (P < 0.001). There was no statistically significant differences between adult rabbit, and 'typical squamous' human biopsies (range 51-65%), results which suggest potential use of a rabbit model to study changes in human oesophageal tissue.

Adult↗

PubMed1992

Characterization through a data display of the different cellular responses in X-irradiated small intestine.

Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points.

Animals↗

PubMed1992

Early effects on the morphology of mouse small intestine of single or combined modality treatment with hyperthermia and X-irradiation.

This study describes the effects of hyperthermia and X-irradiation on the morphological appearance of normal, at risk tissues in the ileum of the mouse. The early morphological effects 1 day after a combined modality treatment are compared with those due to either hyperthermia or X-irradiation given alone. The response was assessed qualitatively and semiquantitatively using scanning electron microscopy and a villous scoring technique. Early post-irradiation effects on topography did not differ significantly from those observed after small intestine exteriorisation without treatment. The villous scores for the combined modality treatments reflected greater damage than would be expected from the sum of villous scores for each modality treatment on its own. This suggests that the combined modality treatment had a synergistic or enhancing effect. A 4 hour time interval between the two treatments did not seem to reduce the enhancing effect. Further studies are required to investigate the effects of fractionated combined treatment.

Animals↗

PubMed1992

Relationship between villous shape and mural structure in neutron irradiated small intestine.

Previous work on irradiation of mouse small intestine has assessed the changes produced by counting crypts/microcolonies, scoring villous shape or examining morphological changes in specific parts of the wall. This paper used scanning and transmission electron microscopy to study the effects of whole body irradiation with 5 Gy neutrons on the surface and internal features of the intestinal wall of CFLP mice, 1 day, 3 days and 7 days after treatment. Empirical scores from the ultrastructural findings were inserted into a Morphological Index display calculated from analytical data based on cell counts and area measurements obtained from resin histology sections. The final data display showed that the neutron irradiation produced marked structural changes in different cells and tissues by 1 day. These changes were maximal at 3 days with substantial improvement by 7 days. When this data display was compared with scores taken from scanning electron microscopy of the mucosal surface, the change in villous shape from erect fingerlike projections to lower profiles less suited to absorption was seen to correlate more with changes in the smooth muscle than with the epithelial cryptal compartment.

Animals↗

PubMed1991

Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm.

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.

Animals↗

PubMed1991

Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.

Adult↗