Creative partnering in perioperative education.
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Education, Nursing↗
Biomedical subjects
S Millard
Publications and source records attributed to S Millard.
Ablation of atrial fibrillation in the rapid pacing canine model using a multi-electrode loop catheter.
OBJECTIVES: This investigation details our experience using a loop catheter to ablate atrial fibrillation (AF) in dogs. BACKGROUND: Atrial fibrillation is the most common arrhythmia and has significant morbidity. Maintenance of normal sinus rhythm (NSR) after conversion in many patients is still a challenge. METHODS: A multi-electrode loop catheter was used to create linear atrial lesions to ablate AF in a rapid atrial pacing model in 29 dogs. Rhythm status was assessed over a six-month recovery period, after which tissue analysis was performed. RESULTS: Acute conversion to NSR or atrial tachycardia (AT) was achieved in 90% of cases. Six of 26 conversions occurred after only left atrial (LA) lesions, and two after just right atrial lesions. Sixteen (62%) of 26 lesions that resulted in AF conversion were in the LA, and 11 of these 16 conversions occurred during a lesion connecting the mitral ring to the pulmonary veins. Acute conversion rate was similar with ring and coil electrodes, but AT was more frequent with coil electrodes (63% vs. 31%). At six months 80% of dogs were in NSR, 14% were in AT, and 7% remained in AF. There was an average reduction in P-wave amplitude of 64 +/- 26% after power application. Tissue analysis revealed transmural contiguous lesions when final outcome was NSR, and nontransmural/noncontiguous lesions where AF persisted. CONCLUSIONS: Multi-electrode loop catheters can create contiguous transmural lesions in either atrium to safely and effectively ablate AF and provide a stable long-term rhythm outcome in this dog model. The left atrium appears to be the dominant chamber that sustains AF. Atrial tachycardia is a frequent acute outcome with coil electrodes.
Animals↗
Time course of left atrial mechanical recovery after linear lesions: normal sinus rhythm versus a chronic atrial fibrillation dog model.
INTRODUCTION: The extent of left atrial (LA) mechanical function recovery after creation of linear lesions using the loop catheter has not been determined. METHODS AND RESULTS: LA mechanical function was assessed before and after linear lesions using transthoracic two-dimensional and Doppler echocardiography in two groups: (1) normal, which consisted of eight healthy dogs in normal sinus rhythm (NSR); and (2) atrial fibrillation (AF), which consisted of nine dogs in spontaneous AF for 6 months following rapid pacing-induced AF. NSR was restored with linear lesions in all AF dogs. All animals were in NSR 5 months after linear lesions. In the normal dogs, the maximal velocity of the transmitral flow "A" wave was reduced by 42% during the first week postablation and by 24% at 5 months versus preablation. At 5 months, no differences in LA function were noted between the normal and the AF group for all measured Doppler parameters. At 5 months, the LA systolic area in AF dogs was reduced by 40% (preablation 12.9 +/- 2.9 cm2, postablation 7.6 +/- 1.2 cm2; P < 0.01) and in the normal dogs by 21% (preablation 10.0 +/- 0.9 cm2, postablation 7.8 +/- 1.2 cm2; P < 0.02), being the same in both groups within 3 months of recovery. CONCLUSION: The creation of linear lesions with the loop catheter does not result in LA expansion. In normal dogs, LA mechanical activity is reduced for 3 weeks postablation. The time course of LA mechanical function recovery is the same for the AF and the NSR dogs, and it is complete at 3 months postablation. At 5 months, LA systolic function parameters in both groups are reduced by 24% versus the preablation values of the normal dogs. Linear lesions result in a significant reduction in LA size.
Animals↗
Sulfides impair short chain fatty acid beta-oxidation at acyl-CoA dehydrogenase level in colonocytes: implications for ulcerative colitis.
The disease process of ulcerative colitis (UC) is associated with a block in beta-oxidation of short chain fatty acid in colonic epithelial cells which can be reproduced by exposure of cells to sulfides. The aim of the current work was to assess the level in the beta-oxidation pathway at which sulfides might be inhibitory in human colonocytes. Isolated human colonocytes from cases without colitis (n = 12) were exposed to sulfide (1.5 mM) in the presence or absence of exogenous CoA and ATP. Short chain acyl-CoA esters were measured by a high performance liquid chromatographic assay. 14CO2 generation was measured from [1-14C]butyrate and [6-14C]glucose. 14CO2 from butyrate was significantly reduced (p < 0.001) by sulfide. When colonocytes were incubated with hydrogen sulfide in the presence of CoA and ATP, butyryl-CoA concentration was increased (p < 0.01), while crotonyl-CoA (p < 0.01) and acetyl-CoA (p < 0.01) concentrations were decreased. These results show that sulfides inhibit short chain acyl-CoA dehydrogenase. As oxidation of n-butyrate governs the epithelial barrier function of colonocytes the functional activity of short chain acyl-CoA dehydrogenase may be critical in maintaining colonic mucosal integrity. Maintaining the functional activity of dehydrogenases could be an important determinant in the expression of ulcerative colitis.
Acyl Coenzyme A↗
Colonic luminal hydrogen sulfide is not elevated in ulcerative colitis.
It has been proposed that the reduction in n-butyrate oxidation by colonic epithelial cells observed in ulcerative colitis may be related to exposure to reduced forms of sulfur derived from dissimilatory sulfate reduction by luminal microflora. This study aims to compare stool sulfide concentrations in control and colitic subjects. Control subjects had significant colorectal disease excluded by virtue of their selection. Patients with ulcerative colitis were stratified by disease extent and activity, and by salicylate drug use. Stool sulfide was measured using a direct spectrophotometric method on NaOH (free sulfide) and zinc acetate (total sulfide) stool slurries. Fifteen control and 19 colitic subjects were studied. There was no significant difference in stool sulfide between control and colitic patients (free sulfide, control = 0.52 (0.17), colitic = 0.45 (0.10), t = 0.36, P = 0.71, total sulfide, control = 1.33 (0.21), colitic = 0.96 (0.15), t = 1.44, P = 0.16). Disease extent or activity did not significantly influence stool sulfide. These results do not support a primary etiologic role for luminal sulfide in ulcerative colitis.
Colitis, Ulcerative↗
Hydrogen sulphide produces diminished fatty acid oxidation in the rat colon in vivo: implications for ulcerative colitis.
BACKGROUND: Several lines of evidence suggest a possible role for reduced forms of sulphur (including sulphide) in ulcerative colitis. The aims of this study were to assess the metabolic profile of colonic epithelial cells after treatment in vivo with hydrogen sulphide and correlate this with mucosal histological appearances. METHODS: Adult Sprague-Dawley rats had antegrade Roux-en-Y colostomies fashioned to allow access to the 'in-flow' bowel. Animals were treated with 2 mL sodium hydrosulphide (10, 20, 30 mmol/L) or saline control twice daily via the stoma for four (acute experiments) and 90 (chronic experiments) days. Isolated colonic epithelial cell suspensions prepared from such animals were incubated in the presence of [1-14C]-labelled n-butyrate (5 mmol/L) or [6-14C]glucose (5 mmol/L). Metabolic performance was measured radiometrically (14CO2 production) and enzymatically (ketone body production and lactogenesis). The histological appearances of treated mucosa were scored for acute inflammatory changes. RESULTS: There was a highly significant reduction in 14CO2 production from both n-butyrate and glucose in all groups compared to the control in both acute and chronic experiments. There was no difference between groups with respect to histological appearance and no evidence of acute inflammation in any specimen. CONCLUSIONS: Sodium hydrosulphide impairs rat colonic epithelial metabolic performance in vivo, but does not produce mucosal inflammation.
Animals↗
Effect of sulphide on short chain acyl-CoA metabolism in rat colonocytes.
BACKGROUND: It has been proposed that the diminished n-butyrate oxidation observed in ulcerative colitis may be the result of sulphide induced inhibition of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity. AIM: To examine the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in vitro with sodium hydrogen sulphide (NaHS). METHODS: Isolated rat colonic epithelial cell suspensions were incubated for 10 minutes in the presence of [1-14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried out both in the presence and the absence of exogenous CoA and ATP. Metabolic performance was assessed by 14CO2 production and by acyl-CoA ester production measured by HPLC with ultraviolet detection. RESULTS: Results are given as mean (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP, treatment with NaHS significantly diminished 14CO2 production (control 0.97 (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight cells/min, p = 0.0019), was associated with an increase in butyryl-CoA concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28) mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p = 0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02) mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p = 0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10 minutes was not significantly different between control and sulphide treated incubations. There were no significant differences in acyl-CoA ester profiles observed when cells were incubated in the absence of exogenous CoA and ATP. CONCLUSIONS: These results support the view that sulphides inhibit n-butyrate oxidation in colonic epithelial cells by inhibiting short chain acyl dehydrogenation of activated fatty acids.
Acyl Coenzyme A↗
Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.
Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.
Alleles↗
Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis.
BACKGROUND: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS: To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives. METHODS AND SUBJECTS: Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed. RESULTS: In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value.
Acetamides↗
Selective inhibition of fatty acid oxidation in colonocytes by ibuprofen: a cause of colitis?
Ibuprofen is associated with initiation or exacerbation of ulcerative colitis. As ibuprofen selectively inhibited fatty acid oxidation in the liver or caused mitochondrial damage in intestinal cells, its effect on substrate oxidation by isolated colonocytes of man and rat was examined. Ibuprofen dose dependently (2.0-7.5 mmol/l) and selectively inhibited 14CO2 production from labelled n-butyrate in colonocytes from the proximal and distal human colon (n = 12, p = < 0.001). Glucose oxidation was either unaltered or increased. Because short chain fatty acid oxidation is the main source of acetyl-CoA for long chain fatty acid synthesis, the inhibition of prostaglandin synthesis by ibuprofen in the colonic mucosa could also occur at this level. Because the concentrations of ibuprofen that can be attained in the human colon are not known, conclusions drawn from current dosages are tentative. The inhibition of fatty acid oxidation by ibuprofen may be biochemically implicated in the initiation and exacerbation of ulcerative colitis, manifestation of which would depend on the ibuprofen concentrations reached in the colon.
Aminosalicylic Acids↗
Early recurrent otitis media, language and central auditory processing in children.
The study examines the relationships that exist between early recurrent otitis media, language and central auditory processing in children. A retrospective case-control experimental design was employed and ten subjects were allocated to each of the two research groups, namely children with a history of early recurrent otitis media (research group 1) and children without a history of early recurrent otitis media (research group 2). The children in both research groups were in grade one and turning 7 years old. The language and central auditory processing of the subjects were assessed using the Clinical Evaluation of Language Function (Wiig & Semel, 1980) and the Willeford Battery of Central Auditory Function (Willeford, 1974). The results showed that the language and central auditory processing of the children with a history of early recurrent otitis media were significantly poorer than that of their disease-free peers. The results stress the importance of vigorous identification and management programmes for children with a history of early recurrent otitis media.
Audiometry↗
Characterization of NK-2 binding sites in rabbit lung tissue.
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Animals↗
Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis.
BACKGROUND: Mercaptides (sodium hydrogen sulfide and sodium methanethiol) and mercapto-fatty acid (sodium mercaptoacetate) are reducing agents that help to maintain anaerobic conditions in the colonic lumen. The metabolic effect of these agents on n-butyrate and glucose oxidation in human colonocytes is unknown. METHODS: Isolated human colonocytes were prepared from 31 colectomy specimens, and generation of oxidative metabolites from [1-14C]n-butyrate and [6-14C]glucose was measured in the presence and absence of reducing agents. Injury to cells was judged by diminished production of metabolites. RESULTS: The injurious action of mercaptides at all sites of the colon was of the order of sodium hydrogen sulfide > methanethiol > mercaptoacetate. Significant inhibition of n-butyrate (< 0.005) but not glucose oxidation was observed with sodium hydrogen sulfide in the ascending colon, splenic flexure, and rectosigmoid region. Hydrogen sulfide more significantly inhibited fatty acid oxidation in the rectosigmoid than in the ascending colon (P < 0.02). CONCLUSIONS: Metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active ulcerative colitis, and the increased production of sulfide in ulcerative colitis suggests that the action of mercaptides may be involved in the genesis of ulcerative colitis.
Colitis, Ulcerative↗
Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis?
1. Isolated colonic epithelial cells of the rat were incubated for 40 min with [6-14C]glucose and n-[1-14C]butyrate in the presence of 0.1-2.0 mmol/l NaHS, a concentration range found in the human colon. Metabolic products, 14CO2, acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells was judged by diminished production of metabolites. 2. Oxidation of n-butyrate to CO2 and acetoacetate was reduced at 0.1 and 0.5 mmol/l NaHS, whereas glucose oxidation remained unimpaired. At 1.0-2.0 mmol/l NaHS, n-butyrate and glucose oxidation were dose-dependently reduced at the same rate. 3. To bypass short-chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation, ketogenesis from crotonate was measured in the presence of 1.0 mmol/l NaHS. Suppression by sulphide of ketogenesis from crotonate (-10.5 +/- 6.1%) compared with control conditions was not significant, whereas suppression of ketogenesis from n-butyrate (-36.00 +/- 5.14%) was significant (P = < 0.01). Inhibition of FAD-linked oxidation was more affected by NaHS than was NAD-linked oxidation. 4. L-Methionine (5.0 mmol/l) significantly redressed the impaired beta-oxidation induced by NaHS. Methionine equally improved CO2 and ketone body production, suggesting a global reversal of the action of sulphide. 5. Sulphide-induced oxidative changes closely mirror the impairment of beta-oxidation observed in colonocytes of patients with ulcerative colitis. A hypothesis for the disease process of ulcerative colitis is that sulphides may form persulphides with butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal inflammation.
Animals↗
Lipogenesis from n-butyrate in colonocytes. Action of reducing agent and 5-aminosalicylic acid with relevance to ulcerative colitis.
Cell membranes of colonic epithelial cells (CEC) in ulcerative colitis show structural abnormalities which are specific to the disease and which suggest impaired lipogenesis in CECs. Lipogenesis from [1-14C]-n-butyrate, the chief oxidative fuel of colonic epithelial cells, was measured in isolated CECs under control conditions, with or without glucose and in the presence of mercaptoacetate, a major reducing agent in the colonic lumen. Glucose significantly (p < 0.01) stimulated lipogenesis from [1-14C]-butyrate which was reversed by 5 mM mercaptoacetate. Mercaptoacetate significantly diminished CEC thiolase activity (EC 2.3.1.9). 5-Aminosalicylic acid reversed the adverse effects of mercaptoacetate in the saponifiable fraction of extracted lipids. Changes in lipogenesis due to colonic luminal reducing agents would affect the barrier function of CECs a feature relevant to the disease process of ulcerative colitis.
Aminosalicylic Acids↗
Emotional responses to infertility. Understanding patients' needs.
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Adaptation, Psychological↗