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Biomedical subjects

G L Telford

Publications and source records attributed to G L Telford.

At least 19 recordsLinked to original sources
PubMed2001

Effects of intestinal transplantation on postprandial motility and regulation of intestinal transit.

BACKGROUND: The effects of intestinal transplantation on gut motility have not been completely defined. In this study we examine the effects of ileal transplantation on ileal smooth muscle contractility, together with gastroduodenal emptying, intestinal flow, and transit rates in a canine model of short-gut syndrome. METHODS: Animals (n = 22) were instrumented with strain gauge transducers, collection cannulae, and infusion catheters to assess motility, intestinal flow and transit rates, and gastroduodenal emptying. Ten animals served to define normal parameters. Six animals underwent a 70% resection of the proximal small intestine to serve as short-gut controls. Six animals underwent removal of a 100-cm segment of the ileum, with cold storage, and autotransplantation the following day combined with a 70% resection of proximal bowel. RESULTS: Transplant animals exhibited delayed gastroduodenal emptying, reduced intestinal flow rates, and postprandial phasic contractions that were similar to short-gut controls. However, transplant animals experienced rapid intestinal transit compared with short-gut controls (4.8 +/- 0.4 cm/min vs 2.0 +/- 0.3 cm/min; mean +/- SEM; P <.05). CONCLUSIONS: The transplanted intestine, even with 18 hours of cold storage, exhibits a relatively normal postprandial motor response. However, adaptive responses of the transplanted intestine, such as regulation of intestine transit, may be impaired by neuromuscular injury associated with denervation or ischemia.

Animals↗
PubMed2001

Effect of surgical alteration of the rat gastrointestinal tract on the growth and development of Hymenolepis diminuta.

Eight groups of rats were used to study the involvement of the enteric (ENS) and central (CNS) nervous systems in the development of Hymenolepis diminuta using surgical intestinal transection, or CNS denervation, or both procedures. The transection procedure was used to isolate the ENS of the small intestine from either orad and/or caudal portions of the alimentary system, while the CNS denervation was used to eliminate direct visceral efferent inputs from the CNS. Nine days after the surgical procedures, all rats were infected with 35 cysticercoids of H. diminuta. On 20 days postinfection, the infection intensity, tapeworm dry weight, tapeworm morphology, intestine length, and intestinal wet weight were recorded. Only the combination of the duodenal and ileal transections with a CNS denervation reduced infection intensity and prevented the increased intestinal length normally observed in infected rats. In contrast, none of the various intestinal transection procedures alone or CNS denervation alone had any effect on the survival, ability to produce oncospheres or morphology of the tapeworms. In conclusion, tapeworm survival is decreased when both CNS and ENS inputs into the small intestine are altered or absent.

Animals↗
PubMed2000

Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion.

Microvascular endothelial cells play a key role in inflammation by undergoing activation and recruiting circulating immune cells into tissues and foci of inflammation, an early and rate-limiting step in the inflammatory process. We have previously [Binion et al., Gastroenterology112:1898-1907, 1997] shown that human intestinal microvascular endothelial cells (HIMEC) isolated from surgically resected inflammatory bowel disease (IBD) patient tissue demonstrate significantly increased leukocyte binding in vitro compared to normal HIMEC. Our studies [Binion et al., Am. J. Physiol.275 (Gastrointest. Liver Physiol. 38):G592-G603, 1998] have also demonstrated that nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) normally plays a key role in downregulating HIMEC activation and leukocyte adhesion. Using primary cultures of HIMEC derived from normal and IBD patient tissues, we sought to determine whether alterations in iNOS-derived NO production underlies leukocyte hyperadhesion in IBD. Both nonselective (N(G)-monomethyl-L-arginine) and specific (N-Iminoethyl-L-lysine) inhibitors of iNOS significantly increased leukocyte binding by normal HIMEC activated with cytokines and lipopolysaccharide (LPS), but had no effect on leukocyte adhesion by similarly activated IBD HIMEC. When compared to normal HIMEC, IBD endothelial cells had significantly decreased levels of iNOS mRNA, protein, and NO production following activation. Addition of exogenous NO by co-culture with normal HIMEC or by pharmacologic delivery with the long-acting NO donor detaNONOate restored a normal leukocyte binding pattern in the IBD HIMEC. These data suggest that loss of iNOS expression is a feature of chronically inflamed microvascular endothelial cells, which leads to enhanced leukocyte binding, potentially contributing to chronic, destructive inflammation in IBD.

Cell Adhesion↗
PubMed2000

Nitric oxide production is diminished in colonic circular muscle from acquired megacolon.

PURPOSE: Nitric oxide modulates human colonic smooth muscle function. To determine whether nitric oxide production is altered in colon from acquired megacolon, we measured cholinergic nerve-mediated contractions in vitro before and after inhibition of nitric oxide synthase. METHODS: Intramural nerves in circular smooth muscle from histologically normal colon (n = 12) and acquired megacolon (n = 3) were activated by electrical field stimulation. RESULTS: In controls blockade of nitric oxide synthase by N(G)-Nitro-L-Arginine induced increases (P < 0.05) in amplitude of contractions; these increases in amplitudes were blocked by L-Arginine (analysis of variance; P < 0.05). By contrast, blockade of nitric oxide synthase did not increase amplitudes of contractions with circular smooth muscle from acquired megacolon. An immediate phasic contraction was blocked by atropine sulfate. CONCLUSIONS: The results support the concept that nitric oxide production modulates cholinergic nerve-mediated contractions in normal colonic circular muscle, whereas acquired megacolon is associated with altered release of this inhibitory neurochemical. Potential explanations include depletion of tissue L-Arginine, decreased capacity to recycle citrulline to arginine, or decreased release of vasoactive intestinal peptide from circular smooth muscle in acquired megacolon.

Aged↗
PubMed2000

Total antioxidant capacity of colon in patients with chronic ulcerative colitis.

It has been proposed that oxidative stress is involved in the pathophysiology of ulcerative colitis. We have reported the depletion of the nonenzymatic antioxidant, glutathione, in colon from active and inactive ulcerative colitis. The colon contains several biochemically linked antioxidant systems. We hypothesized that diminished total antioxidant capacity in active ulcerative colitis would be associated with increased colonic lipid peroxidation. This study was designed to determine total antioxidant capacity and lipid hydroperoxide levels using colon obtained at surgery from controls (N = 16; 4 females, 12 males; mean age 70 years), and active and inactive ulcerative colitis (N = 15; 3 females, 12 males; mean age 39). Total antioxidant capacity of control colon was higher in muscularis externa compared to the mucosal-submucosal layer (P < 0.05). There were no differences in colonic total antioxidant capacity or lipid hydroperoxide levels comparing control colon to inactive and active ulcerative colitis. The results did not support depletion of tissue total antioxidant capacity by free radicals. Depletion of glutathione in ulcerative colitis may be a specific disorder rather than a secondary defect attributable to global oxidative stress. Nonspecific antioxidant supplements appear unlikely to be beneficial in the treatment of ulcerative colitis.

Adult↗
PubMed2000

Effect of barium sulfate on wound healing in the gastrointestinal tract of the rat.

PURPOSE: To study the effect of barium sulfate on wound healing in the gastrointestinal tract of the rat. MATERIALS AND METHODS: Sixty rats weighing approximately 320 g were divided into four groups: Fifteen control rats had gastric, small-bowel, and colonic incisions; 15 rats had gastric incision; 15 rats had small-bowel incision; and 15 rats had colonic incision. Barium sulfate was placed into the incision before closure in all rats except those in the control group, and the effects were documented clinically and histopathologically for 3 months. Autopsy was performed in five rats from each group at 1, 4, and 12 weeks. The incisions in the rats receiving barium sulfate were compared with those in the control rats. RESULTS: There was no difference in the clinical course (weight gain, activity, and viability) between the control and experimental groups. Early and late autopsy findings and histopathologic grading of healing and inflammatory response were similar for both the control and experimental groups. CONCLUSION: Under the conditions of this study, the effect of barium sulfate on visceral transmural wound healing in the gastrointestinal tract of the rat was minimal.

Abdominal Abscess↗
PubMed1999

Nitric oxide synthase is increased following small intestinal transplantation in the rat.

Transplantation of the small intestine is a neural model that could include extrinsic denervation, loss of intrinsic enteric neurons, or loss of intrinsic neural pathways. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was measured in normal rat ileum, ileum 3 months after resection of the jejunum, and ileum 3 months after isotransplantation of the ileum. The distribution of NADPH diaphorase activity and immunoreactive neuronal nitric oxide synthase were examined. Nicotinamide adenine dinucleotide phosphate diaphorase activity was increased in transplanted ileum (16.5+/-3.5 mU/mg protein) compared to normal controls (6.6+/-0.7) and resection controls (6.8+/-0.6) (P < 0.05, ANOVA). Histologically, NADPH diaphorase activity and immunoreactive nitric oxide synthase appeared increased within nerve cell bodies following transplantation. These findings may represent an adaptive response of the enteric nervous system to extrinsic denervation. Loss of intrinsic neural pathways was not supported as a mechanism.

Analysis of Variance↗
PubMed1998

Distribution of muscarinic receptor subtypes in rat small intestine.

Despite its great promise, small intestinal transplantation in some patients is complicated by difficult postoperative management. The reasons for this are complex. In a rat model of small intestinal transplantation, frequencies of migrating myoelectric complexes during fasting are reduced in ileal isografts and muscarinic receptor density is decreased. We hypothesized that the distribution of muscarinic 1 receptors localized to enteric neurons is altered after small intestinal transplantation. Distal small intestine was orthotopically transplanted in Lewis-to-Lewis donor-recipient combinations. At 3 months, transplanted and normal ileum was obtained to prepare membrane fractions. [N-methyl-3H]Scopolamine served as ligand, while scopolamine methylbromide, pirenzepine, and methoctramine were used in competitive homologous and heterologous displacement experiments. Receptor subtype models were examined by nonlinear regression analysis. In normal and transplanted ileum, heterologous displacement was consistent with three site models (P < 0.05). In normals, the muscarinic 1 receptor subtype was most abundant, with a relative distribution of 69 to 78%. There was a relative distribution of 13 to 16% for muscarinic 3 receptor subtype. After transplantation, the muscarinic 1 subtype decreased to a mean of 45% but the muscarinic 3 subtype increased to a mean of 42%. Using pirenzepine, mean pKD values were not different between the two groups. It is concluded that the decrease in muscarinic 1 receptor subtype after transplantation could be related to neuronal cell loss or to downregulation of the expression of muscarinic 1 receptors. The results did not support defective posttranslational processing of receptor proteins.

Animals↗
PubMed1997

Postprandial motor activity and its relationship to transit in the canine ileum.

BACKGROUND: The purpose of this study was to elucidate the mechanism of reduced intestinal transit rate in the ileum as compared with the jejunum. METHODS: Twenty-one dogs were each instrumented with 12 strain gauge transducers, 2 collection cannulas, and an infusion catheter defining a 100 cm study in the midjejunum (n = 11) and midileum (n = 10). Postprandial motor activity and intestinal transit were measured 1 hour after ingestion of a 650 kcal solid meal. Contractile activity was analyzed by means of computer programs that determine frequency, amplitude, and propagation behavior of circular smooth muscle contractions. RESULTS: Postprandial ileal contractions occurred with greater frequency (13.7 +/- 2.5 versus 11.5 +/- 0.4; p = 0.04) and displayed a higher incidence of propagation (61% +/- 2% versus 44% +/- 3%; p = 0.0001) than jejunal contractions, but traveled at significantly slower rates (1.0 +/- 0.7 cm/sec vs 3.7 +/- 0.9 cm/sec; p = 0.0001). The net result was significantly slower transit in the ileum compared with the jejunum (4.7 +/- 0.7 cm/min versus 13.1 +/- 1.5 cm/min; p = 0.0006). Within each region, transit correlated with parameters of propagating contractions. Stepwise regression of the combined data revealed that contraction velocity was the most important variable determining intestinal transit rate (r = 0.64; p < 0.001). CONCLUSIONS: Contrary to previous thinking, postprandial ileal contractions display a high degree of temporal and spatial organization. Slow ileal transit is mainly due to reduced propagation velocity, which is intrinsic to the circular smooth muscle.

Animals↗
PubMed1997

Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal.

Inflammation suppresses phasic contractile activity in vivo. We investigated whether inflammation also suppresses in vitro phasic contractile activity and, if so, whether this could in part be due to the alteration of specific slow wave characteristics and morphology of the interstitial cells of Cajal (ICC). Circular muscle strips were obtained from normal and inflamed distal canine colon. Inflammation was induced by mucosal exposure to ethanol and acetic acid. The amplitudes of spontaneous, methacholine-induced, substance P-induced, and electrical field stimulation-induced contractions were smaller in inflamed muscle strips than in normal muscle strips. Inflammation reduced the resting membrane potential and the amplitude and duration of slow waves in circular muscle cells. Inflammation did not affect the amplitude of inhibitory junction potentials but did decrease their duration. Ultrastructural studies showed expansion of the extracellular space between circular muscle cells, reduction in the density of ICC and associated neural structures, damage to ICC processes, vacuolization of their cytoplasm, and blebbings of the plasma membrane. We conclude that inflammation-induced alterations of slow wave characteristics contribute to the suppression of phasic contractions. These alterations may, in part, be due to the damage to ICC. Inflammation impairs both the myogenic and neural regulation of phasic contractions.

Acetic Acid↗
PubMed1996

Expression of mRNA for vasoactive intestinal peptide in rat small intestine.

Transplantation of small intestine is a neural model that permits studies of expression of the neuropeptide, vasoactive intestinal peptide, following extrinsic denervation, transection of intrinsic neural pathways, and an ischemic interval. Tissue levels of vasoactive intestinal peptide were examined at 3 months in ileum from a sham operation, in ileum after resection of proximal small intestine, in ileum after resection of proximal small intestine and extrinsic denervation, in ileum after resection of proximal small intestine and 30 min of ischemia, and in ileum obtained 3 months after ileal isografting in Lewis-to-Lewis combinations. Vasoactive intestinal peptide levels were increased in transplanted rat ileum, resection controls, denervation controls, and ischemic controls compared to sham-operated ileum (pANOVA < 0.01). The increased levels of this peptide were highest in denervation controls and lowest in ischemic controls. Northern blot analysis using rat vasoactive intestinal peptide cDNA identified a single 1.7-kb transcript in normal and transplanted rat ileum. The density of vasoactive intestinal peptide transcripts was increased in transplanted ileum (8450 +/- 540) compared to normal ileum (5790 +/- 620) (P < 0.01), and the ratio of this transcript to glyceraldehyde-3-phosphate dehydrogenase density units was also increased in transplanted ileum (0.81 +/- 0.08) compared to normal ileum (0.40 +/- 0.07; P < 0.01). Enhanced transcriptional regulation was the likely mechanism for increased tissue vasoactive intestinal peptide. The increased tissue levels appeared to be a response to extrinsic denervation and transection of intrinsic neural pathways, while an ischemic interval appeared to decrease tissue levels of the peptide.

Animals↗
PubMed1996

Myoelectric activity and absorptive capacity of rat small intestinal isografts.

The effect of transplantation on small intestinal absorption, digestive capacity, myoelectric activity, and morphology was assessed in inbred Lewis rats. Electrodes were sutured to the duodenum and isografted jejunoileum or to the native jejunoileum in controls. The frequency of migrating myoelectric complexes (MMCs) in the duodenum was 3.3 +/- 0.3/hr in controls and 1.8 +/- 0.4/hr in transplants (P < 0.05). MMC frequency in the jejunoileum was 5.1 +/- 1.3/hr in controls and 3.2 +/- 0.9/hr in transplants (P > 0.05). MMCs appeared to migrate from the duodenum to the jejunoileum 80 +/- 3% of the time in controls and 59 +/- 7% of the time in transplant rats (P < 0.05). Absorption in the transplanted jejunoileum demonstrated a 35-40% decrease in glucose and electrolytes absorption. Villus height and number of nuclei per villus was reduced. Intestinal length (dry) was 103 +/- 6 cm for controls and 51 +/- 3 cm for transplant rats (P < 0.05). Brush border sucrase activity was unchanged. We conclude that small intestinal isografts display similar myoelectric activity as controls, but the decreased absorptive capacity and villus height may require longer segments of intestine to be transplanted in order to support normal nutrition.

Animals↗
PubMed1996

Decreased vasoactive intestinal peptide levels and glutathione depletion in acquired megacolon.

We reported decreased vasoactive intestinal peptide levels in acquired megacolon. The origin of altered neuropeptide levels is unknown, but recent work suggested that tissue antioxidants may function as neuroprotectants. Our hypothesis was that altered levels of inhibitory neurotransmitters in human colon are associated with depletion of the tripeptide thiol, glutathione. Normal colon samples (N = 10; from patients 41-80 years old) and acquired megacolon samples (N = 10; from patients 31-98 years old) were obtained at surgery. Vasoactive intestinal peptide levels were decreased in muscularis externa from acquired megacolon (P = 0.01), while there was a modest increase in NADPH diaphorase activity in muscularis externa from megacolon (P = 0.10). Glutathione in acquired megacolon was detectable in muscularis externa from only five specimens (P < 0.05), but was not significantly different (P > 0.05) in the mucosal-submucosal layer. The results supported the presence of vasoactive intestinal peptide and NADPH diaphorase in distinct subpopulations of nerves in human colon. The results also supported the hypothesis that glutathione functions as a neuroprotectant in a subset of patients with acquired megacolon.

Adult↗
PubMed1996

Delayed gastroduodenal emptying is an important mechanism for control of intestinal transit in short-gut syndrome.

PURPOSE: To understand the relative importance of changes in ileal smooth muscle contractility versus alteration of intestinal flow rate as control mechanisms for regulating intestinal transit in a surgical model of short-gut syndrome. METHODS: A model of short-gut syndrome was created by performing a 70% proximal small-bowel resection in dogs. Ten control and 6 animals with short-gut syndrome were instrumented with strain gauge transducers, steel collection cannulas, and a Silastic intraluminal infusion catheter in the midileum. Motor activity was analyzed by computer programs that determine frequency, amplitude, and propagation behavior of postprandial contractions. Perfusions of 14C-polyethylene glycol and bolus injection of 3H-polyethylene glycol were used to determine intestinal flow and transit rates. Total gastroduodenal emptying was determined using a 14C-polyethylene glycol-labelled meal. RESULTS: Postprandial contraction frequency was decreased in animals with short-gut syndrome, but other significant changes in amplitude, mean area, and propagation behavior of postprandial ileal contractions were not seen. Gastroduodenal emptying and mean intestinal flow rates were markedly slower in animals with short-gut syndrome, as were intestinal transit rates. CONCLUSIONS: In this model of short-gut syndrome, the major adaptive change is decreased intestinal flow rate, related to delayed gastroduodenal emptying. The spatial organization of ileal contractions does not change substantially aside from a change in frequency which can be accounted for by transection of the intestinal wall.

Animals↗
PubMed1995

Expression of mRNA for vasoactive intestinal peptide in normal human colon and during inflammation.

The availability of colon provides a ready source of human neurons. Among the products of nerve cell bodies, vasoactive intestinal peptide is a neuropeptide that serves as a marker of non-adrenergic, non-cholinergic inhibitory nerves in colon. These nerves have been proposed to be involved in regulation of immune function, secretion, and smooth muscle function. In previous work, we identified decreased tissue levels of vasoactive intestinal peptide in a disorder of chronic colonic mucosal inflammation, ulcerative colitis. We hypothesized that diminished gene expression of vasoactive intestinal peptide could result in decreased tissue levels of this neuropeptide. Sigmoid colon was obtained at surgery from controls (n = 6) and patients with ulcerative colitis (n = 6). Vasoactive intestinal peptide mRNA was quantified by Northern blot hybridization and tissue levels of vasoactive intestinal peptide were determined by radioimmunoassay. Tissue vasoactive intestinal peptide was decreased only in the mucosal-submucosal layer of ulcerative colitis (p = .02). There was a single 1.7 kbase vasoactive intestinal peptide transcript identified in both control colon and ulcerative colitis. Normalized vasoactive intestinal peptide mRNA levels were increased by 260% in ulcerative colitis compared to controls (p < .01). These observations suggest that decreased vasoactive intestinal peptide gene expression or abnormal post-transcriptional processing are not primary defects in this disorder of chronic inflammation. The findings support the alternative hypothesis that axonal degeneration in ulcerative colitis could result in increased expression of neuronal vasoactive intestinal peptide mRNA.

Adult↗
PubMed1995

Prevention of blood exposure. Body and facial protection.

Regardless of the specific clinical setting in the operating room, it is clear that better protection of all personnel is an appropriate objective in the current environment. Better protection through improved PPE and modification of operational practices is essential. A prompt response to blood contact when it does occur is likewise appropriate. With conscientious applications of methods to reduce blood exposure, it is hoped that the operating room can become a safer place with respect to occupational infections from bloodborne pathogens.

Blood-Borne Pathogens↗
PubMed1995

Bloodborne pathogen transmission from healthcare worker to patients. Legal issues and provider perspectives.

Health-care providers have an obvious, primary obligation to patients. Yet providers also have obligations to the public health (society), their institutional or individual self-interests, and their employees (fellow health-care workers). These obligations contain inherent conflicts, and attempts to reconcile the conflicts often perpetuate contradictions. This article identifies and discusses some of the moral and legal bases of these conflicts.

Blood-Borne Pathogens↗