Biomedical subjects

C A Edwards

Publications and source records attributed to C A Edwards.

At least 73 records · Page 4Linked to original sources

PubMed1992

Interactive image-guided neurosurgery.

Interactive image-guided (IIG) surgery involves the synchronal display of the tip of a surgical device on preoperative scans. This display allows the surgeon to locate the present surgical position relative to the final site of surgical interest. We have developed a technique for IIG surgery device based on a six-degree-of-freedom articulated arm. Design accuracy for the arm is less than 0.1 mm and the present implementation has a submillimetric accuracy. The display can show the surgical position on any tomographic image set with simultaneous display on up to three image sets. Laboratory results and clinical applications are discussed.

Brain↗

PubMed1992

Effect of the dietary fibre content of lifelong diet on colonic cellular proliferation in the rat.

The effect of the fibre content of lifelong (18 months) diets on proximal and distal colonic cellular proliferation and short chain fatty acid (SCFA) content was investigated in 40 rats. Rats were fed a low fibre diet (17 g/kg non-starch polysaccharides NSP) or the stock diet (133 g/kg NSP). The higher fibre fed rats had increased caecal and colonic total contents (p < 0.001) and SCFAs than the low fibre fed rats (caecal SCFAs: higher fibre rats 96.4 (6.8) mumol/g wet weight v low fibre 22.7 (3.0): p < 0.001, colonic SCFAs: higher fibre 52.3 (3.1) mumol/g wet weight v low fibre 6.9 (2.2) mumol/g wet weight: p < 0.001). Cellular proliferation was increased in the proximal colon (bromodeoxyuridine labelling index, higher fibre 9.3 v low fibre 8.4 p < 0.05; flow cytometry, % cells in S phase higher fibre diet 7.9 v low fibre 6.9; p < 0.01) and there was a shift of proliferating cells to a higher region in each crypt. There was no significant difference in the percentage of cells in S phase in the distal colon of rats in both diet groups. The proliferative zone, however, was expanded in the distal colon of the higher fibre diet fed rats. This study indicates that long term higher fibre intake in rats is associated with a modest increase in cellular proliferation in the proximal colon but not the distal colon.

Animals↗

PubMed1992

Comparison of the effects of ispaghula and wheat bran on rat caecal and colonic fermentation.

The effects of ispaghula and wheat bran on the contents of the caecum and proximal and distal colon of the rat were investigated to identify any differences that might account for their effects on colonic motility. Rats fed diets supplemented with 5% ispaghula and 10% wheat bran for 28 days were killed and the contents of the gut collected. Caecal and colonic content wet and dry weight and short chain fatty acid (SCFA) content were measured. In additional in vitro fermentations in batch cultures of mixed rat caecal bacteria with ispaghula and bran, SCFA production was monitored over 24 hours. Both ispaghula and wheat bran increased faecal weight but ispaghula was more effective. Ispaghula resulted in greater and more liquid contents, with a characteristic pattern of SCFA production (higher propionic acid) maintained throughout the colon. In contrast, wheat bran affected only the caecum and faeces. SCFA content and wet and dry weight in the proximal and distal colon were unaffected by wheat bran. Caecal butyrate was characteristically higher in wheat bran fed rats but ispaghula produced higher butyrate in the distal colon. In contrast, ispaghula seemed to be fermented more quickly in vitro than wheat bran. Thus, wheat bran has a portion that is rapidly fermented and an inert residue that may stimulate motility. Ispaghula seems to be fermented throughout the colon but maintains a high water content which dilutes the luminal contents.

Animals↗

PubMed1992

Effect of short-chain fatty acids on contractile activity and fluid flow in rat colon in vitro.

The effect of short-chain fatty acids (SCFAs) on the contractile activity and fluid output of the large bowel of the rat was studied using an isolated segment of cecum and colon, mounted in vitro. The rate of contractile activity per minute in the proximal, mid, and distal regions of the colon was depressed by luminal infusion of associated SCFAs either as a mixture (acetic, propionic, and butyric) or individually (100 mM/pH = 4.1, in each case). Dose responses were observed for the individual fatty acids, with the 100 mM solutions eliciting a more prominent reduction in colonic motor activity than that induced by 10 mM. Neither the Na salt of the fatty acids nor an acidified Krebs solution (pH = 4.1) inhibited contractile activity or fluid output. No reduction in the rate of contractile activity was observed in the cecum with any test solutions, except 100 mM butyric acid. The data suggest that SCFAs inhibit smooth muscle contractility and resultant fluid transit.

Animals↗

PubMed1992

A universal system for interactive image-directed neurosurgery.

Stereotactic methods confer great accuracy to intracranial target localization, but require strict adherence to a complex program of mechanical and computational maneuvers. A computerized, articulated, localizing 'arm' has been developed that frees the neurosurgeon of these constraints and provides a completely intuitive, 'user-friendly' interface. This universal system is independent of whatever localizing fiducial system is selected. The arm may be sterilized for intracranial use. A variety of intraoperative end effectors may be selected. The patient's CT/MR/PET scans are loaded into computer memory and a three-dimensional shaded surface wireframe diagram of the patient's head is displayed simultaneously with up to 3 independent sets of cross-referenced CT/MR/PET scan images on the intraoperative video screen. The arm's endpoint location and the directional vector are shown as cursors on the relevant scan slices, and change continuously as the surgeon moves the arm. Because the information is continuously updated, an unlimited number of targets and trajectories may be displayed throughout the operation. The arm has an ultimate design accuracy for end-point localization to within 0.1 mm throughout a target volume of 40 x 40 x 40 cm. The tested application accuracy of the first prototype model is 0.31 mm. In clinical use during 30 surgeries, its real-world application accuracy is 0.9 mm. This system provides stereotactic accuracy and universally compatible, intuitive, interactive operation.

Biopsy↗

PubMed1991

Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40.

After antigenic stimulation of T lymphocytes, genes essential for proliferation and immune function, such as the interleukin-2 (IL-2) gene, are transcriptionally activated. In both transient transfections and T lymphocyte-specific in vitro transcription, the homeodomain-containing protein Oct-1 participated in the inducible regulation of transcription of the IL-2 gene. Oct-1 functioned in this context with a 40-kilodalton protein called Oct-1-associated protein (OAP40). In addition to interacting specifically with DNA, OAP40 reduced the rate of dissociation of Oct-1 from its cognate DNA-binding site, suggesting that a direct interaction exists between Oct-1 and OAP40.

Amino Acid Sequence↗

PubMed1990

Effect of oral nicardipine on anorectal function in normal human volunteers and patients with irritable bowel syndrome.

Paired controlled studies were performed in 10 normal volunteers and 32 patients with irritable bowel syndrome to investigate the effect of the calcium channel blocker nicardipine, on the responses of the anorectum to rectal distension and a meal. Nicardipine was administered orally in standard (20 mg) and sustained-release (30 mg twice a day) formulations. In normal volunteers standard nicardipine had no significant effect on the rectal responses to distension but did significantly reduce the postprandial motility index (P less than 0.05). In the patients with irritable bowel syndrome, standard nicardipine caused a significant reduction in distension-induced rectal motor activity (P less than 0.05) and increased the rectal sensory thresholds for desire to defecate and discomfort (P less than 0.02). Slow-release nicardipine caused a significant reduction in distension-induced activity (P less than 0.05) but did not alter rectal sensory thresholds. Both formulations of nicardipine significantly reduced the postprandial motility index (P less than 0.05) and symptoms (P less than 0.05). In conclusion, this study confirms that calcium channel blockers may be useful in the management of irritable bowel syndrome.

Administration, Oral↗

PubMed1990

Dietary fiber: in vitro methods that anticipate nutrition and metabolic activity in humans.

Gravimetric measurement of dietary fiber (DF) gives no indication of the biological function of any particular fiber. This study describes simple methods based on dialysis and fermentation that enable a hierarchy of fibers to be described for each of the major actions of fiber along the gastro-intestinal tract: nutrient absorption, sterol metabolism, cecal fermentation, and fecal bulking. These results were compared with previous metabolic studies with the same fiber isolates in humans. DF that modifies nutrient absorption can be identified by using dialysis studies, whereas identifying DF that modifies sterol metabolism, cecal fermentation, and fecal weight requires formulas that incorporate dialysis and fermentation results. Results from dialysis and fermentation predicted the action of wheat bran, pectin, guar, gum arabic, carboxymethylcellulose, gellan, tragacanth, xanthan, and karaya in humans and generated anomalous results for karaya and tragacanth. These methods could form the basis of techniques that would enable a screening of novel and processed fibers before studies in animals, including humans.

Bile Acids and Salts↗

PubMed1990

HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF.

The coordinate expression of genes during development and differentiation is thought to be accomplished by common transcription factors operating on the promoters of families of coexpressed genes. HNF-1 is a transcriptional factor involved in the expression of genes in the liver and was originally defined as playing a major role in coordinating the expression of the linked fibrinogen genes. We have isolated cDNA clones for HNF-1 using oligonucleotides prepared to the sequence of the purified protein. The sequence of HNF-1 shares homeo domain, as well as short acidic and basic sequences with the POU family of transcriptional activators. Peptides from the protein interacting with the albumin proximal element, or B box (APF), and the factor interacting with the alpha 1-antitrypsin promoter (LF-B1) are found in the predicted sequence of HNF-1. HNF-1 mRNA is not present in the dedifferentiated hepatoma variant, C2, but reappears upon selection for gluconeogenesis coincident with the re-expression of liver-specific genes. Finally, the mRNA is not present in somatic cell hybrids in which liver-specific gene expression is extinguished. In contrast to earlier published results, we find that in addition to being present in the liver, HNF is expressed in the kidney, intestine, and spleen, but not in other tissues. This pattern of expression mirrors the complex pattern of expression of many genes, such as alpha-fetoprotein, alpha 1-antitrypsin, and fibrinogen, whose promoters contain HNF-1 sites. These data indicate that HNF-1 is a more broadly acting transcription factor than has been indicated by previous work.

Albumins↗

PubMed1989

Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects.

Islet amyloid peptide (or diabetes-associated peptide), the major component of pancreatic islet amyloid found in type-2 diabetes, has been identified by electron-microscopic immunocytochemistry in pancreatic B-cells from five non-diabetic human subjects, and in islets from five type-2 diabetic patients. The greatest density of immunoreactivity for islet amyloid peptide was found in electron-dense regions of some lysosomal or lipofuscin bodies. The peptide was also localised by quantification of immunogold in the secretory granules of B-cells, and was present in cytoplasmic lamellar bodies. Acid phosphatase activity was also demonstrated in these organelles. Immunoreactivity for insulin was found in some lysosomes. These results suggest that islet amyloid peptide is a constituent of normal pancreatic B-cells, and accumulates in lipofuscin bodies where it is presumably partially degraded. In islets from type-2 diabetic subjects, amyloid fibrils and lipofuscin bodies in B-cells showed immunoreactivity for the amyloid peptide. Abnormal processing of the peptide within B-cells could lead to the formation of islet amyloid in type-2 diabetes.

Adolescent↗

PubMed1989

Effect of bile acid on anorectal function in man.

The effects of rectal infusions (500 ml) of deoxycholic acid (1 mmol/l, 3 mmol/l) or normal saline on basal anorectal motility and responses to rectal distension were studied in 11 normal volunteers. Deoxycholic acid (1 mmol/l) did not alter anorectal motor patterns under basal conditions but reduced the rectal volumes required to induce a desire to defecate (deoxycholic acid 76 (12) ml v saline 123 (12) ml; mean (SEM) p less than 0.01), and to produce anal relaxation (deoxycholic acid 83 (14) ml v saline 152 (24) ml; p less than 0.05) and perception of the rectal balloon (deoxycholic acid 56 (10) ml v saline 104 (17) ml; p less than 0.01) that were sustained for the period of distension (1 min). Seven of 10 subjects could not tolerate an infusion of 3 mmol/l deoxycholic acid. Between two and 30 minutes after the start of the infusion they experienced an extreme urge to defecate which was associated with large amplitude pressure waves in the rectal channels (amplitude 30 (5) mmHg, duration 0.7 (0.1) min, frequency 1.7 (0.4)/min). Such contractions were never seen during saline infusion. Thus, rectal infusion of deoxycholic acid at physiological concentrations increases the sensitivity of the rectum to distension, and promotes an urgent desire to defecate in normal subjects.

Adolescent↗

PubMed1989

Effects of hypothyroidism, tri-iodothyronine and glucocorticoids on growth hormone responses to growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe-Lys-NH2.

The aim of this study was to investigate the role of thyroid hormones and glucocorticoids on GH secretion. Secretion of GH in response to GH-releasing hormone (GHRH) (5 micrograms/kg) was markedly (P less than 0.001) decreased in hypothyroid rats in vivo (peak GH responses to GHRH, 635 +/- 88 micrograms/l in euthyroid rats vs 46 +/- 15 micrograms/l in hypothyroid rats). Following treatment with tri-iodothyronine (T3; 20 micrograms/day s.c. daily for 2 weeks) or cortisol (100 micrograms/day s.c. for 2 weeks) or T3 plus cortisol, a marked (P less than 0.01) increase in GH responses to GHRH was observed in hypothyroid rats (peak GH responses, 326 +/- 29 micrograms/l after T3 vs 133 +/- 19 micrograms/l after cortisol vs 283 +/- 35 micrograms/l after cortisol plus T3). In contrast, none of these treatments modified GH responses to GHRH in euthyroid animals. Hypothyroidism was also associated with impaired GH responses to the GH secretagogue, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). Secretion of GH in response to GHRP-6 in vivo was reduced (P less than 0.01) in hypothyroid rats (peak GH responses, 508 +/- 177 micrograms/l in euthyroid rats vs 203 +/- 15 micrograms/l in hypothyroid rats). In-vitro studies carried out using monolayer cultures of rat anterior pituitary cells derived from euthyroid and hypothyroid rats showed a marked impairment of somatotroph responsiveness to both GHRP-6 and somatostatin in cultures derived from hypothyroid rats. In summary, our data suggest that thyroid hormones and glucocorticoids influence GH secretion by modulating somatotroph responsiveness to different GH secretagogues.

Animals↗

PubMed1988

Does adding fibre to a low energy, high carbohydrate, low fat diet confer any benefit to the management of newly diagnosed overweight type II diabetics?

The effect of supplementing a low energy (roughly 5.0 MJ), high carbohydrate (180 g), low fat (roughly 25 g) diet with 10-15 g of either cereal fibre or guar gum was investigated in 24 newly diagnosed overweight non-insulin-dependent (type II) diabetics. The patients were divided into three treatment groups: one received a low fibre control diet throughout the study period of 20 weeks and the other received two supplements of cereal fibre and guar gum in a crossover manner. The nutrient content of the diets was kept constant throughout. Though patients taking the low fibre diet showed a smaller reduction in fasting plasma glucose concentrations over the first eight weeks than patients taking a high fibre diet, this difference was not evident at the end of 20 weeks; reductions in weight and glycated haemoglobin values were similar for each dietary regimen throughout the trial. There was little evidence that supplementing a low energy, high carbohydrate diet with fibre confers any therapeutic benefit to type II diabetics and no evidence that taking fibre as viscous polysaccharides is any more beneficial to overweight diabetics than taking a similar fibre supplement as cereal. On the contrary, guar gum caused more abdominal discomfort and flatulence than the other diets.

Blood Glucose↗

PubMed1988

Impaired colonic fermentation of carbohydrate after ampicillin.

The aim of this study was to investigate the effect of ampicillin on the ability of the human colon to ferment carbohydrate. The effect of ingesting a drink containing 20 g of lactulose on stool output and breath hydrogen production was measured in 13 normal volunteers before and during administration of ampicillin (2 g/day). Small bowel and whole gut transit times were also measured to exclude any direct effect of ampicillin on motor activity. Ingestion of lactulose did not increase stool weight or frequency under control conditions, but during administration of ampicillin, lactulose caused increases in stool weight (p less than 0.02) and frequency (p less than 0.01), in the percentage of unformed stools (p less than 0.001), and in the excretion of galactose and fructose in stool samples collected from 2 volunteers. Administration of ampicillin also significantly reduced the area under the breath hydrogen profile (p less than 0.03). Mouth-to-cecum transit of the lactulose drink was prolonged during ampicillin ingestion (p less than 0.01) but there was no significant change in the whole gut transit time. These results suggest that ampicillin impairs colonic fermentation of carbohydrate and a diet high in unabsorbable carbohydrate increases the risk of antibiotic-associated diarrhea.

Adult↗

PubMed1988

Inactivation of lipid-enveloped viruses in labile blood derivatives by unsaturated fatty acids.

Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid-enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of greater than or equal to 10(4) tissue culture infectious doses (TCID50) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60-100% retention of AHF activity, was achieved with oleic, 11-eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma-linolenic, palmitic, and arachidic acids and another fat-soluble compound previously reported to inactivate virus, butylated hydroxytoluene, were less effective. A long chain mono- but not a di- or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of greater than or equal to 10(3.4) TCID50. The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 degrees C for 4-6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 degrees C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous lipid and/or albumin.

Antiviral Agents↗

PubMed1988

Evidence that growth hormone depletion and uncoupling of the regulatory protein of adenylate cyclase (Ns) both contribute to the desensitization of growth hormone responses to growth hormone-releasing factor.

Recent data suggest that the response of GH to GH-releasing factor (GRF) is reduced following prior exposure to high concentrations of GRF. However, it is unknown whether this is due to alterations in GRF receptors, adenylate cyclase activity or the size of a GRF-releasable storage pool of GH. In order to clarify these questions we have compared the effects of pretreatment with GRF (10 nmol/l every 2 h for 12 h) with those of pretreatment with somatostatin (SRIF; 1 mumol/l), forskolin (10 mumol/l) and GRF plus SRIF (10 nmol/l and 1 mumol/l added together) on the subsequent responses of GH to GRF (1 pmol/l-10 nmol/l), cholera toxin (10 nmol/l), 3-isobutyl-l-methylxanthine (IBMX) (100 mumol/l) and forskolin (10 mumol/l). Experiments were performed on 4-day monolayer cultures of rat anterior pituitary cells. The cells were pretreated with test substances every 2 h for 12 h and incubated with GRF or forskolin for 3 h. Per cent maximal (Bmax) GH responses to GRF (10 nmol/l) were reduced after pretreatment with both GRF (control, 173% of basal; GRF, 25% of basal; P less than 0.001) and forskolin (98% of basal; P less than 0.001), but were increased after pretreatment with SRIF (246% of basal; P less than 0.02). However, GH responses after pretreatment with GRF plus SRIF were not significantly different from those of the control.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1988

Ultrastructural observations on bacterial invasion in cementum and radicular dentin of periodontally diseased human teeth.

In this study the bacterial invasion in root cementum and radicular dentin of periodontally diseased, caries-free human teeth was examined. In addition, structural changes in these tissues, which could be related to the bacterial invasion, were reported. Twenty-one caries-free human teeth with extensive periodontal attachment loss were studied by light and scanning electron microscopy. At the base of the gingival pocket, bacteria were found in the spaces between remnants of Sharpey's fibers and their point of insertion in the cementum. In teeth that had been scaled and root planed, most of the root cementum had been removed. Bacterial invasion was found in the remaining root cementum. The invasion seemed to start as a localized process, often involving only one bacterium. In other areas bacteria were present in lacunar defects in the cementum. These lacunae extended into the radicular dentin. In 11 teeth bacteria had invaded the dentinal tubules. Most bacteria were located in the outer 300 microns of the dentinal tubules, although occasionally they were found in deeper parts. In two of the nontreated teeth, bacteria were detected on the pulpal wall. No correlation was found between the presence of bacterial invasion and the absence of radicular cementum. No bacteria were found in the portion of the root located apically to the epithelial attachment. These data are in agreement with our results from cultural studies of the bacterial flora in these structures. It was also demonstrated that in spite of meticulous scaling and root planning and personal oral hygiene, bacterial plaque remained present on radicular surfaces. Both the invaded dentinal tubules and the lacunae could act as bacterial reservoirs from which recolonization of treated root surfaces occurs. From these reservoirs bacteria could also induce pulpal pathoses. Since these bacterial reservoirs are not eliminated by conventional mechanical periodontal treatment, it seems appropriate to combine mechanical periodontal therapy with the use of chemotherapeutic agents.

Bacteria↗

PubMed1988

Do viscous polysaccharides slow absorption by inhibiting diffusion or convection?

Viscous polysaccharides such as guar gum delay absorption probably by impairing the access of luminal contents to the absorptive epithelium. Measurements of the electrical resistivity of saline solutions were carried out to determine if guar gum (0.5, 0.75 and 1 per cent w/v), in concentrations which impaired absorption in vitro, delayed diffusion of solutes or inhibited convection of luminal contents. Our results indicated that guar had no effect on the mobility of ions in a completely unstirred solution but delayed the time taken for saline solutions of different resistivity to achieve complete mixing, when they were brought into contact inside a vessel, which was rotated at a constant speed. The time taken to achieve complete mixing was directly related to the viscosity of the guar solutions. The effect of intestinal contraction on the absorption of glucose was simulated in an in vitro model, consisting of a length of dialysis tubing, alternately contracted at each end. Movement of glucose out of the dialysis tubing was increased by increasing the rate of contraction. The incorporation of guar gum into the solution prevented the rise in glucose uptake produced by increasing the rate of contraction. These effects suggest that guar probably reduces absorption by resisting the convective effects of intestinal contractions.

Dietary Fiber↗