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1.  Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro 
The Journal of General Physiology  1977;69(5):655-666.
The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (ρO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; ρO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it.
PMCID: PMC2215083  PMID: 864433
2.  Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro 
AIM: To observe and compare the effects of phytoestrogen genistein, resveratrol and 17β-estradiol on the tonic contraction and the phasic contraction of isolated gallbladder muscle strips and to study the underlying mechanisms.
METHODS: Isolated strips of gallbladder muscle from guinea pigs were suspended in organ baths containing Kreb’s solution, and the contractilities of strips were measured before and after incubation with genistein, resveratrol and 17β-estradiol respectively.
RESULTS: Similar to 17β-estradiol, genistein and resveratrol could dose-dependently inhibit the phasic contractile activities, they decreased the mean contractile amplitude and the contractile frequencies of gallbladder muscle strips, and also produced a marked reduction in resting tone. The blocker of estrogen receptor ICI 182780 failed to alter the inhibitory effects induced by genistein and resveratrol, but potassium bisperoxo (1, 10 phenanthroline) oxovanadate bpV (phen), a potent protein tyrosine phosphatase inhibitor, markedly attenuated the inhibitory effects induced by genistein and resveratrol. In calcium-free Kreb’s solution containing 0.01 mmol/L egtazic acid (EGTA), genistein and resveratrol inhibited the first phasic contraction induced by acetylcholine (ACh), but did not affect the second contraction induced by CaCl2. In addition, genistein, resveratrol and 17β-estradiol also could reduce the contractile responses of ACh and KCl, and shift their cumulative concentration-response curves rightward.
CONCLUSION: Phytoestrogen genistein and resveratrol can directly inhibit the contractile activity of isolated gallbladder muscle both at rest and in response to stimulation. The mechanisms responsible for the inhibitory effects probably due mainly to inhibition of tyrosine kinase, Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from sarcoplasmic reticulum (SR), but were not related to the estrogen receptors.
PMCID: PMC2739951  PMID: 18756606
Phytoestrogen; Estradiol; Gallbladder; Smooth muscle; Ca2+ channel
3.  Effect of pharmacologically induced smooth muscle activation on permeability in murine colitis. 
Mediators of Inflammation  2003;12(1):21-27.
BACKGROUND: Both intestinal permeability and contractility are altered in inflammatory bowel disease. Little is known about their mutual relation. Therefore, an in vitro organ bath technique was developed to investigate the simultaneous effects of inflammation on permeability and smooth muscle contractility in different segments of the colon. METHODS AND MATERIALS: BALB/c mice were exposed to a 10% dextran sulphate sodium drinking water solution for 7 days to induce a mild colitis, while control mice received normal tap water. Intestinal segments were placed in an oxygenated organ bath containing Krebs buffer. Permeability was measured by the transport of the marker molecules 3H-mannitol and 14C-polyethyleneglycol 4000. Contractility was measured through a pressure sensor. Smooth muscle relaxation was obtained by salbutamol and l-phenylephrine, whereas contraction was achieved by carbachol and 1-(3-chlorophenyl)-biguanide. RESULTS: The intensity of mucosal inflammation increased throughout the colon. Also, regional differences were observed in intestinal permeability. In both normal and inflamed distal colon segments, permeability was diminished compared with proximal colon segments and the non-inflamed ileum. Permeability in inflamed distal colon segments was significantly decreased compared with normal distal segments. Pharmacologically induced relaxation of smooth muscles did not affect this diminished permeability, although an increased motility positively affected permeability in inflamed and non-inflamed distal colon. CONCLUSIONS: Inflammation and permeability is inversely related. The use of pro-kinetics could counteract this disturbed permeability and, in turn, could regulate the disturbed production of inflammatory mediators.
PMCID: PMC1781592  PMID: 12745545
4.  Inflammatory Bowel Disease in the Obese Patient 
Obesity is becoming increasingly more common among patients with inflammatory bowel disease. In this review, we will explore the epidemiological trends of inflammatory bowel disease, the complex interplay between the proinflammatory state of obesity and inflammatory bowel disease, outcomes of surgery for inflammatory bowel disease in obese as compared with non-obese patients, and technical concerns pertaining to restorative proctocolectomy and ileoanal pouch reservoir, stoma creation and laparoscopic surgery for inflammatory bowel disease in obese patients.
PMCID: PMC3311491  PMID: 23204939
Obesity; Crohn's disease; ulcerative colitis; inflammatory bowel disease; laparoscopy; restorative proctocolectectomy
5.  Commonly used intravenous anesthetics decrease bladder contractility: An in vitro study of the effects of propofol, ketamine, and midazolam on the rat bladder 
This study was designed to test the hypothesis that propofol, ketamine, and midazolam could alter the contractile activity of detrusor smooth muscle.
Materials and Methods:
Four detrusor muscle strips isolated from each rat bladder (n = 12) were placed in 4 tissue baths containing Krebs-Henseleit solution. The carbachol (10 −8to 10−4mol/L)-induced contractile responses as well as 5, 10, 20, 30, 40, 50 Hz electrical field stimulation (EFS)-evoked contractile responses of the detrusor muscles were recorded using isometric contraction measurements. After obtaining basal responses, the in vitro effects of propofol, ketamine, midazolam (10−5 to 10−3 mol/L), and saline on the contractile responses of the detrusor muscle strips were recorded and evaluated.
All the 3 drugs reduced the carbachol-induced and/or EFS-evoked contractile responses of rat detrusor smooth muscles in different degrees. Midazolam (10−4 to 10−3 mol/L) caused a significant decrease in the contractile responses elicited by either EFS or carbachol (P=0.000−0.013). Propofol (10−3mol/L) caused a decrease only in EFS-evoked contractile responses (P=0.001−0.004) and ketamine (10−3mol/L) caused a decrease only in carbachol-induced contractile responses (P=0.001−0.034).
We evaluated the effects of the 3 different intravenous anesthetics on detrusor contractile responses in vitro and found that there are possible interactions between anesthetic agents and detrusor contractile activity. The depressant effects of midazolam on the contractile activity were found to be more significant than ketamine and propofol. Despite the necessity of further studies, it could be a piece of wise advice to clinicians to keep the probable alterations due to intravenous anesthetics in mind, while evaluating the results of urodynamic studies in children under sedation.
PMCID: PMC2978435  PMID: 21116355
Bladder; smooth muscle contractility; propofol; ketamine; midazolam
6.  Fulminant Clostridium difficile Enteritis after Proctocolectomy and Ileal Pouch-Anal Anastamosis 
Clostridium difficile (C. difficile) infection of the small bowel is very rare. The disease course is more severe than that of C. difficile colitis, and the mortality is high. We present a case of C. difficile enteritis in a patient with ileal pouch-anal anastamosis (IPAA), and review previous case reports in order to better characterize this unusual condition.
PMCID: PMC2633454  PMID: 19197378
7.  The Contractility of Isolated Rat Atrial Tissue during Hypoxia is Better Preserved in a High- or Zero-Glucose Environment than in a Normal Glucose Environment 
Hyperglycemia is known to be associated with an increase in mortality in myocardial infarction and intensive care patients despite the fact that glucose metabolism plays a central role in myocardial protection. We studied the effect of different glucose levels (22 mM L-1; 5.5 mM L-1; and 0 mM L-1) on the contractile reserve of isolated rat atrial myocardium during and after hypoxia.
We observed the contraction of isolated rat atrium strips caused by electrical-field stimulation in a modified Krebs-Henseleit Buffer (KHB) organ bath oxygenated with 95% O2 + 5% CO2 at 37°C. We applied two periods of hypoxia and two periods of reoxygenation. Three glucose concentrations were used in the buffer to study the effect of glucose (high- n=6; normal- n=7; and zero-glucose n=6). The effect of isoproterenol 1 μM L-1 was tested during the second ischemic period.
The main finding was that both a zero-glucose (27.8 ± 5.9 vs. 14.7 ± 3 % of baseline tension) and a high-glucose environment (38.5 ± 14 vs. 14.7 ± 3 % of baseline tension) had a positive effect in terms of better contractility than the normal-glucose buffer during both the first (p=0.00062) and the second ischemic period (31.2 ± 5.9 % zero-glucose vs. 14.7 ± 4.2 normal-glucose vs. 35.3 ± 15.9% high-glucose p=0.0038).
Both zero-glucose and high-glucose environments resulted in a better contractile reserve in isolated rat atrial myocardium during hypoxia than in a normal one. The exact clinical relevance of this observation is, at present, unclear.
PMCID: PMC3614748  PMID: 23675108
glucose environment; mechanical function; contractility; hypoxia; glucose; isolated rat atrial myocardium
8.  Role of capsule endoscopy in inflammatory bowel disease 
Videocapsule endoscopy (VCE) has revolutionized our ability to visualize the small bowel mucosa. This modality is a valuable tool for the diagnosis of obscure small bowel Crohn’s disease (CD), and can also be used for monitoring of disease activity in patients with established small-bowel CD, detection of complications such as obscure bleeding and neoplasms, evaluation of response to anti-inflammatory treatment and postoperative recurrence following small bowel resection. VCE could also be an important tool in the management of patients with unclassified inflammatory bowel disease, potentially resulting in reclassification of these patients as having CD. Reports on postoperative monitoring and evaluation of patients with ileal pouch-anal anastomosis who have developed pouchitis have recenty been published. Monitoring of colonic inflammatory activity in patients with ulcerative colitis using the recently developed colonic capsule has also been reported. Capsule endoscopy is associated with an excellent safety profile. Although retention risk is increased in patients with small bowel CD, this risk can be significanty decreased by a routine utilization of a dissolvable patency capsule preceding the ingestion of the diagnostic capsule. This paper contains an overview of the current and future clinical applications of capsule endoscopy in inflammatory bowel disease.
PMCID: PMC3921500  PMID: 24574792
Small bowel videocapsule endoscopy; Crohn’s disease; Pouchitis; Indeterminate inflammatory bowel disease; Ileal pouch-anal anastomosis; Patency capsule
9.  Umbilical artery tone in maternal obesity 
The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI).
Sections of umbilical artery were obtained from umbilical cord samples immediately after delivery and mounted for isometric recording in organ tissue baths under physiological conditions. Cumulative additions of 5-Hydroxytryptamine (5-HT) and Prostaglandin F-2alpha (PgF2alpha) were added in the concentration range of 1 nmol/L to 10 micromol/L. Control vessels were exposed to Krebs physiological salt solution (PSS) only. The resultant effects of each drug addition were measured using the Powerlab hardware unit.
5-HT exerted a significant effect on human umbilical artery tone at concentrations of 100 nmol/L, 1 micromol/L, and 10 micromol/L in normal (n = 5; P < 0.05) and obese (n = 5; P < 0.05) women. The contractile effect was significantly greater in vessels from obese women {Mean Maximum Tension (MMT) = 4.2532 g} than in those from women of normal BMI (MMT = 2.97 g; P < 0.05). PgF2alpha exerted a significant contractile effect on vessels at 1 micromol/L and 10 micromol/L concentrations when compared with controls (n = 5; P < 0.05). There was a non-significant trend towards an enhanced tone response in vessels from obese women (MMT = 3.02 g; n = 5), in comparison to vessels from women of a normal BMI (MMT = 2.358 g; n = 5; P > 0.05).
These findings support the hypothesis that endogenous regulation of umbilical artery tone is altered in association with maternal obesity. This may be linked to the cardiovascular effects of secretory products of adipose tissue, with implications for the feto-maternal circulation.
PMCID: PMC2649927  PMID: 19161625
10.  The Effect of Oxytocics on the "Ca-Deficient" Uterus  
If the excised, parturient rabbit uterus is repeatedly treated with a Krebs solution free from Ca, its tension in a tetanus drops gradually, and in 15 to 30 minutes becomes zero. We call such a uterus "Ca-deficient." The uterus in this condition has a high threshold, it is non-propagating, "inexcitable," fails to respond to oxytocics in a characteristic fashion, but retains maximum contractility. As Ca is gradually restored to the Krebs, these lost qualities return in a graded fashion and tension of the tetanized uterus becomes a log function of the [Ca]. If the [Ca] is kept low, i.e. 1/10 to 1/20 of the normal, tetanic tension is small but steady, and the preparation offers a full scale of tension increment for the measurement of oxytocic potency. Keeping the stimulus and the [Ca] constant, excitability (measured by tension increment) is a log function of the drug concentration. The recovery of excitability by restoring Ca to the Ca-deficient uterus is strongly temperature-dependent. The Ca-deficient uterus is a useful preparation for the study of the mechanism of regulation. When its excitability is partially recovered by Ca, the electrically stimulated uterus becomes an excellent tool for the quantitative measurement of oxytocic potency.
PMCID: PMC2194971  PMID: 13812445
11.  Effect of theophylline on membrane potential and contractile force in hamster diaphragm muscle in vitro. 
Journal of Clinical Investigation  1986;77(2):638-640.
Theophylline enhances the force of diaphragmatic contraction and delays fatigue. The mechanism is not known, but recent evidence suggests it may act at the cell membrane. To test this hypothesis, we studied the effect of theophylline on resting membrane potential and tension in hamster diaphragm cells. Muscle strips were obtained from five adult hamsters and placed in Krebs solution, aerated with 95% O2, 5% CO2. Resting membrane potential was measured using 3-M KCl-filled glass microelectrodes; 15-22 fibers in each strip were sampled. Force frequency curves (twitch to 100 Hz) were obtained. The muscle bath was then changed to one containing 100 mg/liter (0.55) theophylline. Resting membrane potential was -76 +/- 3 mV (mean +/- S.D.) in Krebs solution and increased to -85 +/- 3 mV (P less than 0.01) with added theophylline. Tension increased from 5% (at 100 Hz) to 20% (at 10 Hz) with theophylline. Hyperpolarization indicates an increase in intracellular to extracellular potassium concentration. Net potassium outflow occurs with each contraction, causing the cell membrane to become depolarized with repeated contractions, ultimately leading to fatigue. The hyperpolarization of the skeletal muscle cell membrane observed with theophylline may play an important role in prolonging time to fatigue.
PMCID: PMC423404  PMID: 3944272
12.  Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway 
Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone.
Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10-10-10-5 M) ± EP1 antagonist. Significance was established using Student t test and P < 0.05.
Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 ± 0.88 to 4.43 ± 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 ± 0.70 vs. 4.43 ± 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 ± 0.01 to 1.97 ± 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist.
In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.
PMCID: PMC3714408  PMID: 23875097
Gastrointestinal motility; Intestine, small; Lubiprostone; Receptors, prostaglandin E
13.  Hemeoxygenase-1 inhibits human myometrial contractility via carbon monoxide and is upregulated by progesterone during pregnancy. 
Journal of Clinical Investigation  1998;101(5):949-955.
Nitric oxide was proposed as an endogenous inhibitor of myometrial contractility during pregnancy. Carbon monoxide (CO) like nitric oxide increases cGMP and is generated during the degradation of heme to biliverdin IX by hemeoxygenases (HO). Here we report that the expression of both HO-1 (inducible) and HO-2 (constitutive) were > 15-fold higher in pregnant myometrium compared to nonpregnant myometrium (n = 4, P < 0.001, P < 0.005, respectively). Moreover, the activation of the HO-CO pathway by the HO inducer, hemin (10 microM), completely inhibited spontaneous contractility (n = 3). Oxytocin-stimulated contractions (n = 5) were also significantly reduced (P < 0.05) in myometrial strips mounted for isometric recording under 2 g tension in Krebs solution. Reverse transcription-PCR analysis revealed that mRNA encoding HO-1 and HO-2 was undetected in explant cultures of nonlaboring pregnant myometrium under basal conditions, however, exposure to progesterone, but not estradiol-17beta, induced the expression of HO-1 and HO-2 mRNAs. Progesterone also significantly induced HO-1 protein synthesis (n = 4, P < 0.001) while estradiol-17beta had no effect (n = 4). In term (37-42-wk gestation) nonlaboring myometrial explants, CO production was stimulated by progesterone (10(-6) M) (n = 2) and hemin (10 microM) (n = 3) after 2 h of incubation and the effect of hemin was inhibited by 1 h of preincubation with the HO inhibitor tin protoporphyrin IX (20 microM). This study clearly demonstrates the expression of HO in the human myometrium and shows that its induction produces CO that limits uterine contractility in pregnant myometrium indicating a role for the HO-CO-cGMP pathway in the maintenance of the quiescent state of the uterus during pregnancy.
PMCID: PMC508644  PMID: 9486963
14.  Family History and Serology Predict Crohn’s Disease after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis 
Diseases of the colon and rectum  2007;51(1):100-108.
About 5 to 10 percent of patients undergoing ileal pouch-anal anastomosis with a diagnosis of ulcerative colitis are subsequently diagnosed with Crohn’s disease. Preoperative predictors for Crohn’s disease post-ileal pouch anal-anastomosis have not been prospectively defined.
Two hundred thirty-eight consecutive patients with ulcerative colitis or indeterminate colitis undergoing ileal pouch anal-anastomosis were prospectively enrolled into a longitudinal database. Clinical factors were assessed perioperatively. Serum drawn pre-operatively was assayed for anti-Saccharomyces-cerevisiae, anti-outer membrane porin-C, anti-CBir1, and perinuclear antineutrophil cytoplasmic antibody using enzyme-linked immunosorbent assay. Crohn’s disease was defined by small-bowel inflammation proximal to the ileal pouch or a perianal fistula identified at least 3 months after ileostomy closure. Predictors were assessed in a multivariate Cox proportional hazards model to predict the rate of Crohn’s disease after ileostomy closure.
Sixteen patients (7 percent) were diagnosed with Crohn’s disease; median time to Crohn’s disease was 19 months (range, 1-41 months). Significant factors for postoperative Crohn’s disease after ileal pouch anal-anastomosis included family history of Crohn’s disease (hazard ratio 8.4, 95 percent confidence interval (CI) 2.96-24.1, p<0.0001) and anti-Saccharomyces-cerevisiae -IgA seropositivity (hazard ratio 3.14, 95 percent CI 1.1-9.81, p=0.04). Crohn’s disease developed in only 8 of 198 (4 percent) patients without these predictors vs. 8 of 40 (20 percent) in those with at least one of these factors (p=0.002). The cumulative risk of Crohn’s disease among patients with 2 risk factors (67 percent) was higher than in patients with either risk factor (18 percent) or neither risk factor (4 percent, p<0.001).
Patients with ulcerative colitis and indeterminate colitis with a family history of Crohn’s disease or preoperative anti-Saccharomyces-cerevisiae-IgA seropositivity are more likely to be diagnosed with Crohn’s disease after ileal pouch anal-anastomosis.
PMCID: PMC2442922  PMID: 18085333
Ileal pouch-anal anastomosis; Crohn’s disease; ulcerative colitis; inflammatory bowel disease; indeterminate colitis; serology; pANCA; ASCA; OmpC
15.  Cannabinoids and the gastrointestinal tract 
Gut  2001;48(6):859-867.
The enteric nervous system of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB1 receptors that depress gastrointestinal motility, mainly by inhibiting ongoing contractile transmitter release. Signs of this depressant effect are, in the whole organism, delayed gastric emptying and inhibition of the transit of non-absorbable markers through the small intestine and, in isolated strips of ileal tissue, inhibition of evoked acetylcholine release, peristalsis, and cholinergic and non-adrenergic non-cholinergic (NANC) contractions of longitudinal or circular smooth muscle. These are contractions evoked electrically or by agents that are thought to stimulate contractile transmitter release either in tissue taken from morphine pretreated animals (naloxone) or in unpretreated tissue (γ-aminobutyric acid and 5-hydroxytryptamine). The inhibitory effects of cannabinoid receptor agonists on gastric emptying and intestinal transit are mediated to some extent by CB1 receptors in the brain as well as by enteric CB1 receptors. Gastric acid secretion is also inhibited in response to CB1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. Cannabinoid pretreatment induces tolerance to the inhibitory effects of cannabinoid receptor agonists on gastrointestinal motility. Findings that the CB1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB1 receptors that are precoupled to their effector mechanisms. SR141716A has been reported not to behave in this manner in the myenteric plexus-longitudinal muscle preparation (MPLM) of human ileum unless this has first been rendered cannabinoid tolerant. Nor has it been found to induce "withdrawal" contractions in cannabinoid tolerant guinea pig ileal MPLM. Further research is required to investigate the role both of endogenous cannabinoid receptor agonists and of non-CB1 cannabinoid receptors in the gastrointestinal tract. The extent to which the effects on gastrointestinal function of cannabinoid receptor agonists or antagonists/inverse agonists can be exploited therapeutically has yet to be investigated as has the extent to which these drugs can provoke unwanted effects in the gastrointestinal tract when used for other therapeutic purposes.

PMCID: PMC1728337  PMID: 11358910
16.  Single-Site Laparoscopic Surgery for Inflammatory Bowel Disease 
Background and Objectives:
Single-site laparoscopic colorectal surgery has been firmly established; however, few reports addressing this technique in the inflammatory bowel disease population exist.
We conducted a case-matched retrospective review of 20 patients who underwent single-site laparoscopic procedures for inflammatory bowel disease compared with 20 matched patients undergoing multiport laparoscopic procedures. Data regarding these patients were tabulated in the following categories: demographic characteristics, operative parameters, and perioperative outcomes.
A wide range of cases were completed: 9 ileocolic resections, 7 cases of proctocolectomy with end ileostomy or ileal pouch anal anastomosis, 2 cases of proctectomy with ileal pouch anal anastomosis, and 2 total abdominal colectomies with end ileostomy were all matched to equivalent multiport laparoscopic cases. No single-incision cases were converted to multiport laparoscopy, and 2 single-incision cases (10%) were converted to an open approach. For single-incision cases, the mean length of stay was 7.7 days, the mean time to oral intake was 3.3 days, and the mean period of intravenous analgesic use was 5.0 days. There were no statistically significant differences between single-site and multiport cases.
Single-site laparoscopic surgery is technically feasible in inflammatory bowel disease. The length of stay and period of intravenous analgesic use (in days) appear to be higher than those in comparable series examining outcomes of single-site laparoscopic colorectal surgery, and the outcomes are comparable with those of multiport laparoscopy. This may be because of the nature of inflammatory bowel disease, limiting the benefits of a single-site approach in this population.
PMCID: PMC4035637  PMID: 24960490
Laparoscopy; Single incision; Colorectal; Inflammatory bowel disease
17.  Non-adrenergic non-cholinergic inhibitory innervation shown by electrical field stimulation of isolated strips of human gall bladder muscle. 
Gut  1994;35(3):412-416.
Non-adrenergic non-cholinergic (NANC) inhibitory nerves have been described in all regions of the gastrointestinal tract, but have not been shown previously in the human gall bladder. Electrical field stimulation was used in the presence of various agonists and antagonists to show NANC inhibitory innervation in strips of human gall bladder muscle. Gall bladder strips were set up isometrically in an organ bath containing oxygenated Krebs's solution. Electrical field stimulation was applied at 10 Hz, pulse width 0.3 ms and supramaximal voltage at intervals of 3 to 5 minutes. Of 60 strips that contracted in response to electrical field stimulation, 30 showed relaxation on electrical field stimulation in the presence of either carbachol (5-10 microM) or else atropine (0.5-2 microM) plus cholecystokinin octapeptide (0.01-0.1 microM) or caerulein (0.1 nM) or histamine (5-10 microM). In 22 strips this relaxation was not abolished by guanethidine (2-5 microM) showing the NANC nature of this response. The NANC relaxation was abolished by L-nitroarginine (100 microM) and this effect was partly reversible by L arginine (200 microM). All responses to electrical field stimulation were abolished by tetrodotoxin (0.2-2 microM). These results show for the first time a NANC inhibitory innervation in human gall bladder muscle. The probable neurotransmitter is nitric oxide.
PMCID: PMC1374601  PMID: 8150357
18.  Perforated Small Bowel Diverticulitis After Gastric Bypass 
This report details the management of a patient with perforated acute diverticulitis of the Roux-en-Y loop 4 years after bariatric surgery.
We report a rare case of complicated jejunal diverticulitis in a patient with previous bariatric surgery. Small bowel diverticulosis is generally considered an inoffensive disease. In this report we describe a case of small bowel perforation in an obese subject who had undergone laparoscopic Roux-en-Y gastric bypass.
PMCID: PMC3939332  PMID: 24680159
Small bowel diverticulosis; Gastric bypass; Perforation
19.  Early intervention in intersigmoid hernia may prevent bowel resection—A case report 
Intersigmoid hernia is a rare internal hernia presenting with symptoms of bowel obstruction. Preoperative diagnosis is uncommon but computerised tomography (CT) may show signs to suggest internal hernia.
A 63-year-old female presented with abdominal pain, vomiting and absolute constipation. Examination revealed a tense distended abdomen. A plain abdominal radiograph showed features of small bowel obstruction. Conservative management was initiated without success and a CT scan was performed which showed a dilated distal oesophagus, stomach and small bowel with a non-dilated length of distal ileum and large bowel. Internal hernia was suggested as a possible cause and the patient underwent a laparotomy where a loop of small bowel was found to be strangulated and gangrenous within the intersigmoid fossa. The gangrenous bowel was resected, an end-to-end anastamosis was performed and the fossa was closed. The patient made an uneventful recovery.
Hernias of the sigmoid mesocolon account for 6% of internal hernias with internal hernias themselves causing between 0.2 and 4.1% of intestinal obstruction. This report presents a case of intersigmoid hernia, a rare internal hernia which should be suspected in patients presenting with acute obstruction, no past surgical history and no external hernia. Patients with these symptoms should receive an urgent CT scan to facilitate early surgery and minimise strangulation and prevent bowel resection.
Intersigmoid hernia presents with acute obstruction, no past surgical history and no external hernia. Urgent CT scanning and early surgery may minimise strangulation, conserve bowel and reduce patient morbidity and mortality.
PMCID: PMC3215259  PMID: 22096754
Intersigmoid hernia; Intersigmoid fossa; Sigmoid mesocolon hernia; Internal hernia; Intestinal obstruction
20.  Prolonged Increases in Vein Wall Tension Increase Matrix Metalloproteinases and Decrease Constriction in Rat Vena Cava. Potential Implications in Varicose Veins 
Increased venous hydrostatic pressure plays a role in the pathogenesis of varicose veins. Increased expression of matrix metalloproteinases (MMPs) has been identified in varicose veins. Also, we have shown that MMP-2 inhibits venous contraction. However, the relation between venous pressure, MMP expression and venous dysfunction is unclear. The purpose of this study was to test the hypothesis that prolonged increases in vein wall tension cause overexpression of MMPs and decreased contractility, which in turn promote venous dilation.
Circular segments of inferior vena cava (ICV) were isolated from male Sprague-Dawley rats, and suspended between two wires in Krebs solution. Preliminary vein wall tension-contraction relation showed maximal KCl (96 mmol/L) contraction at 0.5g basal tension, which remained steady with increases in tension up to 2g. Vein segments were subjected to either control (0.5g) or high (2g) basal tension for short (1 hr) or long duration (24 hr). Isometric contraction in response to phenylephrine (Phe, 10−5 mol/L), angiotensin II (AngII, 10−6 mol/L), and KCl was measured. The veins were frozen to determine the expression and localization of MMPs using immunoblots and immunohistochemistry.
In IVC segments subjected to 0.5g tension for 1 hr Phe and AngII produced significant contraction. At higher 2g basal tension for 24 hr, both Phe and AngII contractions were significantly reduced. Reduction in KCl contraction was also observed at high 2g basal tension for 24 hr, suggesting that the reduction in vein contraction is not specific to a particular receptor, and likely involves inhibition of a post-receptor contraction mechanism. In vein segments under 2g tension for 24 hr and treated with TIMP-1, Phe, AngII, and KCl contractions were partially restored, suggesting the involvement of MMPs. IVC immunoblot analysis demonstrated prominent bands corresponding to MMP-2 and MMP-9 protein. High 2g wall tension for 24 hr was associated with marked increase in the amount of MMP-2 and -9 relative to the housekeeping protein actin. There was a correlation between MMP expression and decreased vein contraction. Also, significant increases in MMP-2 and -9 immunostaining were observed in IVC segments subjected to high 2g tension for 24 hr. Both MMP-2 and MMP-9 caused significant inhibition of Phe contraction in IVC segments.
In rat IVC, increases in magnitude and duration of wall tension is associated with reduced contraction and overexpression of MMP-2 and -9. In light of our findings that MMP-2 and -9 promote IVC relaxation, the data suggest that protracted increases in venous pressure and wall tension increase MMPs expression, which in turn reduce venous contraction and lead to progressive venous dilation.
PMCID: PMC2575039  PMID: 18502086
21.  Reoperative Inflammatory Bowel Disease Surgery 
With the advent of restorative proctocolectomy or ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC), not only has there been potential for cure of UC but also patients have enjoyed marked improvements in bowel function, continence, and quality of life. However, IPAA can be complicated by postoperative small bowel obstruction, disease recurrence, and pouch failure secondary to pelvic sepsis, pouch dysfunction, mucosal inflammation, and neoplastic transformation. These may necessitate emergent or expeditious elective reoperation to salvage the pouch and preserve adequate function. Local, transanal, and transabdominal approaches to IPAA salvage are described, and their indications, outcomes, and the clinical parameters that affect the need for salvage are discussed. Pouch excision for failed salvage reoperation is reviewed as well. Relaparotomy is also frequently required for recurrent Crohn's disease (CD), especially given the nature of this as yet incurable illness. Risk factors for CD recurrence are examined, and the various surgical options and margins of resection are evaluated with a focus on bowel-sparing policy. Stricturoplasty, its outcomes, and its importance in recurrent disease are discussed, and segmental resection is compared with more extensive procedures such as total colectomy with ileorectal anastomosis. Lastly, laparoscopy is addressed with respect to its long-term outcomes, effect on surgical recurrence, and its application in the management of recurrent CD.
PMCID: PMC2780117  PMID: 20011321
Restorative proctocolectomy; pouch failure; salvage/reoperation; ulcerative colitis; recurrent Crohn's disease
22.  Changes of smooth muscle contractile filaments in small bowel atresia 
AIM: To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients.
METHODS: Resected small bowel specimens from small bowel atresia patients (n = 12) were divided into three sections (proximal, atretic and distal). Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers α-smooth muscle actin (SMA) and desmin using conventional paraffin sections of the proximal and distal bowel. Small bowel from age-matched patients (n = 2) undergoing Meckel’s diverticulum resection served as controls.
RESULTS: The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue, but the distal bowel was unchanged. Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue. There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel. The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers.
CONCLUSION: Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia.
PMCID: PMC3386323  PMID: 22791945
Small bowel atresia; Enteric nervous system; Smooth muscle; Motility disorder
23.  Importance of CT in Evaluating Internal Hernias after Roux-en-Y Gastric Bypass Surgery 
As the incidence of obesity increases, laparoscopic Roux-en-Y gastric bypass (REYGB) surgery has become a surgical option for many patients. Although the laparoscopic Roux-en Y procedure has been shown to reduce weight and improve diabetes, hyperlipidemia, hypertension and sleep apnea, it is not without significant risks, as more than 10% of patients who undergo this procedure have postoperative GI complications. This is a case of a 51 year old man who presented with diffuse abdominal pain one month status-post Roux-en-Y gastric bypass. CT imaging proved to be crucial in the diagnosis of this pathology with small bowel volvulus and ischemia. We review some key CT findings that can aid clinicians in diagnosing internal hernias since this complication is often misdiagnosed and have a mortality rate of more than 50%.
PMCID: PMC3303317  PMID: 22470668
Roux-en-Y gastric bypass; Internal hernia
24.  Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta 
Korean Journal of Anesthesiology  2010;59(3):196-202.
Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta.
Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10-6 M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10-8 to 10-6 M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10-5 M to 3 × 10-4 M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT).
Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10-3 M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05).
These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging.
PMCID: PMC2946038  PMID: 20877705
Catalase; Diclofenac; Endothelium; Ketorolac; Reactive oxygen species
25.  Evaluation of Thioperamide Effects Using Rat's Trachea Model 
Thioperamide is used as an antagonist to the histamine H3 receptor. During administration of the drug, the trachea may be affected via nasal or oral inhalation. This study was to determine the effects of thioperamide on the trachea of rats in vitro.
We tested the effectiveness of thioperamide on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of thioperamide were performed: 1) effect on tracheal smooth muscle resting tension; 2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; 3) effect of the drug on electrically-induced tracheal smooth muscle contractions.
Thioperamide induced a significant relaxation response at a preparation concentration up to 10-4 M. The drug also inhibited the electrical field stimulation induced spike contraction. However, thioperamide alone had a minimal effect on the basal tension of the trachea at increasing concentrations.
The study indicated that high concentrations of thioperamide might actually antagonize cholinergic receptors and block parasympathetic function of the trachea.
PMCID: PMC3604264  PMID: 23526076
Trachea; Asthma; In vitro; Thioperamide

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