PubMed Health⌕ Search

Biomedical subjects

J J Cullen

Publications and source records attributed to J J Cullen.

At least 37 records · Page 2Linked to original sources

The effect of ethanol on sphincter of Oddi motility in vitro.

Antioxidant enzymes are present in nerves supplying the sphincter of Oddi and regulate its motor function. Oxygen free radicals (O2.-) produce hydrogen peroxide (H2O2) by the action of superoxide dismutase (SOD). Hydroxyl radical (OH.), an important mediator of H2O2 toxicity, oxidizes ETOH. Thus, the aim of our study was determine the effects of ETOH on sphincter of Oddi motility. The sphincter of Oddi was removed from opossums and force transducers recorded tension in its transverse axis. Alcohol (ETOH) was added to the tissue bath in concentrations from 0.1 to 0.4%. OH. was generated by the addition of 0.01% H2O2. Nitric oxide production was inhibited by the addition of 0.3 mM N omega-nitro-L-arginine (L-NNA). H2O2 increased the frequency of sphincter of Oddi contractions. Concentrations of ETOH > 0.3% decreased contractile frequency; however, 0.2% ETOH alone had no affect on the basal frequency of contraction but inhibited the increase in contractile frequency caused by H2O2. L-NNA also increased the contractile frequency; however, this effect was not inhibited by ETOH. We conclude that ETOH attenuates the effect of H2O2 on sphincter of Oddi motility.

Animals↗

Pathophysiology of adynamic ileus.

We hypothesized that the inhibitory neurotransmitters nitric oxide (NO) and vasoactive intestinal peptide (VIP) may play a role in the disrupted gastrointestinal motility of endotoxemia. Strain gauge transducers on the stomach and small intestine of dogs determined interdigestive gastrointestinal motility. Tissue levels of NO synthase and VIP and serum levels of nitrite/nitrate (NO(2)-/NO(3)-) and VIP were measured. Following completion of the baseline studies, dogs were given a single dose of E. coli lipopolysaccharide, 200 microg/kg intravenously, and the studies were repeated for the next three days. Following endotoxin bolus, the migrating motor complex (MMC) was delayed for two days while serum VIP was increased on postendotoxin day 1 and serum NO(2)-/NO(3)- was increased on postendotoxin day 2. There were no changes in gut smooth muscle levels of NO synthase or VIP. We conclude that a single, sublethal dose of endotoxin results in prolongation of the MMC with distinct but independent increases in serum levels of VIP and NO(2)-/NO(3)-.

Animals↗

Gastric contractions, secretions and injury in cold restraint.

The clinical syndrome of stress ulceration has been studied for years using rodent cold restraint stress models, although the pathogenesis of the characteristic focal gastric mucosal lesions produced in these models has been controversial. We used gastric strain gauges to characterize fully the gastric motility effects of a 4-h cold restraint protocol, and we determined the relationship of variations in gastric contents and in gastric contractions to the amount of gastric mucosal injury. Additionally, we examined rat stomachs histologically, and determined the location of focal haemorrhagic mucosal lesions on the mucosal rugae. We found a consistent relationship between force of gastric contractions and gastric mucosal injury, and also a relationship between the initial duration of contractions during restraint and ultimate mucosal injury. Volume, acidity and mucus in the gastric contents were unrelated to mucosal injury. The majority (91%) of the mucosal lesions had some relationship to a rugal fold, with 59% of all lesions at the base of a rugal fold. Thus, the mechanical forces of gastric hypercontractility may contribute to the gastric mucosal injury of rodent cold restraint models.

Animals↗

The role of antioxidant enzymes in the control of opossum sphincter of Oddi motility.

Superoxide rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus terminating the biological activity of NO. The aims of our study were to determine if superoxide alters the motor function of the sphincter of Oddi and to localize the antioxidant enzymes in the sphincter of Oddi. Immunostaining was performed and enzyme activities were measured in the sphincter of Oddi. In physiological experiments, force-displacement transducers recorded tension in the spontaneously contracting sphincter of Oddi and after electrical field stimulation (EFS) of precontracted sphincter of Oddi. Superoxide was generated by the addition of xanthine with xanthine oxidase, superoxide radicals were scavenged by the addition of superoxide dismutase (SOD), and catalase or SOD was inhibited by diethyldithiocarbamic acid. Immunostaining demonstrated SOD and catalase immunoreactivity in ganglia situated at the serosal surface of the circular muscle. Total SOD activity was 202 +/- 12 U/mg. Generation of superoxide or inhibition of SOD increased the contractile frequency and decreased relaxation after EFS. We conclude that superoxide alters sphincter of Oddi motor function, and the presence of superoxide scavenging enzymes in enteric plexuses suggests that they may regulate sphincter of Oddi neuromuscular function by clearing endogenous superoxide.

Animals↗

Effect of hydroxyl radical (OH.) on sphincter of Oddi motility.

Antioxidant enzymes are present in sphincter of Oddi nerves and regulate sphincter of Oddi motor function mediated by NO-releasing nerves. Oxygen free radicals (O2-.) produce hydrogen peroxide (H2O2) by the action of superoxide dismutase (SOD). Hydroxyl radical (OH.) has been shown to play an important role as a mediator of H2O2 toxicity. The aims of our study were to determine the effects of H2O2 on sphincter of Oddi motility and if these effects are mediated by OH.. Adult opossums were sacrificed and the sphincter of Oddi removed and placed in a tissue bath containing oxygenated Krebs solution. Force transducers recorded tension in a transverse orientation at two sites along the sphincter of Oddi specimen. H2O2 was added into the tissue bath at concentrations from 0.01 to 0.5%. O2-. radicals were inhibited by the addition of SOD, while OH. was scavenged by the addition of alcohol (ETOH) or dimethyl sulfoxide (DMSO). H2O2 produced a dose-dependent increase in baseline amplitude, frequency, and peak amplitude of contractions. The effect of 0.01% H2O2 on sphincter of Oddi contractile frequency was inhibited by 0.2% ETOH and DMSO, but not by SOD. We conclude that H2O2 has profound effects on sphincter of Oddi motility and that the actions of H2O2 are probably mediated through OH..

Animals↗

A decade of change in obesity surgery. National Bariatric Surgery Registry (NBSR) Contributors.

BACKGROUND: The International (formerly National) Bariatric Surgery Registry began collecting data in January 1986. The aim of this study was to examine changes in the practice of surgical treatment of severe obesity that occurred during the decade of 1986 through 1995, as observed in the IBSR data. METHODS: All data submitted to the IBSR during the decade were transferred to the IBM mainframe computer for analysis. Characteristics of operative type populations were compared over time using analysis of variance (ANOVA) for age, body mass index (BMI), operative weight and Chi-square (chi2) test for gender. RESULTS: There has been a steady increase over the decade in mean patient weight. The operations used have changed from predominantly 'simple' operations to more frequent use of 'complex' operations. Within the categories of 'simple' and 'complex', an increase in the variety of operations occurred. As a group, patients with 'simple' operations have been heavier, more often male and public pay patients than those who have undergone 'complex' operations. One year weight loss was greater for Roux-en-Y gastric bypass (RGB) than vertical banded gastroplasty (VBG), but follow-up rates were too low to study the relative merits of the operations used. The reported incidence of operative mortality and serious complications (leak with peritonitis, abscess and pulmonary embolism) remained low. CONCLUSIONS: These observations and their implications can be summarized in three statements which relate to action for improved patient care in the beginning of the new century: (1) increasing weight of candidates for surgical treatment during this decade indicates the need for earlier use of operative treatment before irreversible complications of obesity can develop; (2) low risk of obesity surgery, decreasing postoperative hospital stay, and early weight control support the continued and increased use of surgical treatment; (3) continued widespread use of both 'simple' and 'complex' operations with increased modifications of standard RGB and VBG procedures emphasizes the need for standardized long-term data and analyses regarding both weight control and postoperative side-effects.

Adult↗

Gastrointestinal transit during endotoxemia: the role of nitric oxide.

We hypothesized that the disrupted gastrointestinal transit that occurs during endotoxemia is mediated by nitric oxide (NO) and that the inhibition of NO synthesis will normalize intestinal transit and gastric emptying. To determine the effects of endotoxin and steroids on the activity of gastrointestinal smooth muscle NO synthase, rats underwent placement of an intravenous (iv) line and then were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg/iv; LPS, 10 mg/kg/iv + dexamethasone, 3 mg/kg/iv; or saline. The activity of nitric oxide synthase in the stomach, small intestine, and colon were determined by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. To determine intestinal transit and gastric emptying, gavage feedings of nonabsorbable liquid markers were given and rats divided into eight groups: 0.9% NaCl, 1 ml/hr x 5 hr (control); LPS, 10 mg/kg/iv; LPS + N-omega-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg/hr x 5 hr; LPS + N-omega-nitro-D-arginine methyl ester (D-NAME), 10 mg/kg/hr x 5 hr; LPS + L-arginine, 100 mg/kg/hr x 5 hr; LPS + L+NAME + L-arginine; LPS + N-omega-nitro-L-arginine (L-NNA) 10 mg/kg/hr; or LPS + L-NNA + L-arginine. LPS increased the enzymatic activity of both the constitutive and the inducible forms of NO synthase in the small intestine and fundus of the stomach. The acceleration of intestinal transit produced by endotoxemia was reversed with both L-NAME and L-NNA but not with D-NAME. Endotoxemia slowed gastric emptying but this effect was not reversed with either L-NAME or L-NNA. We conclude that NO plays a major role in mediating the rapid intestinal transit during endotoxemia.

Animals↗

Effects of recombinant human hemoglobin on opossum sphincter of Oddi motor function in vivo and in vitro.

Nitric oxide (NO) acts as a nonadrenergic, noncholinergic inhibitor neurotransmitter that regulates sphincter of Oddi (SO) motor function. Hemoglobin blocks NO activity by binding it after it is synthesized. We hypothesized that recombinant human hemoglobin (rHb1.1) affects SO motor function by scavenging NO. Under anesthesia, 12 opossums underwent biliary tract manometry. Following a stabilization period, six animals were given rHb1.1 (0.28 g/kg over 30 min), while six received bovine albumin (0.28 g/kg over 30 min). Recordings were made during the infusion and for 3 hr after the infusion. In an in vitro preparation, force transducers were used to record spontaneous contractions at two sites along the sphincter segment. After a control period, rHb1.1 (0.1 mM) or cyanomethemoglobin (0.1 mM) was added to the tissue bath and recordings continued for another 2 hr. Recombinant human hemoglobin decreased the frequency of contractions, increased resting tone, and blocked the relaxation phase of contraction in vivo. It increased the baseline amplitude, the frequency, and the peak amplitudes of contractions in vitro. Albumin or cyanomethoglobin, which are unable to bind NO, had little effect on SO motor activity. We conclude that rHb1.1 may alter SO motor function by binding endogenous NO.

Analysis of Variance↗

Functional characteristics of canine pylorus in health, with pyloroplasty, and after pyloric reconstruction.

The aim was to determine whether pyloroplasty decreases the strength of pyloric contractions and speeds gastric emptying of solids, while subsequent pyloric reconstruction restores these abnormalities to the control. In conscious dogs, pyloroplasty decreased the strength of pyloroduodenal pressure waves measured with a perfused sleeve sensor [mean +/- SEM pyloroduodenal motility index: control (N = 7) = 1116 +/- 351 mm Hg x sec/10 min; pyloroplasty (N = 7) = 43 +/- 19 mm Hg x sec/10 min; P < 0.05], and caused rapid gastric emptying of solids measured scintigraphically (mean +/- SEM half-emptying time: control = 246 +/- 14 min, pyloroplasty = 176 +/- 16 min; P < 0.05). The frequencies of pyloroduodenal waves and gastric emptying of liquids, however, were unchanged. Pyloric reconstruction restored the postpyloroplasty patterns to the control. In conclusion, pyloroplasty decreased the strength of pyloroduodenal contractions and sped gastric emptying of solids, while pyloric reconstruction restored the altered patterns to the control.

Animals↗

Gastrointestinal myoelectric activity during endotoxemia.

BACKGROUND: Gastrointestinal myoelectric activity during postoperative ileus has been well characterized. However, the common clinical scenario of ileus occurring during and after episodes of sepsis is not well understood. The aim of our study was to determine the effects of a single, sublethal dose of endotoxin on canine gastrointestinal myoelectric activity. METHODS: Eight dogs underwent placement of serosal electrodes on the stomach and small intestine and insertion of a jejunal cannula. After the animals recovered, electrical activity and jejunal mucosal blood flow were determined during fasting and with feeding. Following completion of these baseline studies dogs were given a single, sublethal dose of Escherichia coli lipopolysaccharide (200 g/kg) intravenously, and the studies were repeated daily for 3 consecutive days. RESULTS: Endotoxin resulted in an absence of the interdigestive migrating myoelectric complex for 2 days, a decrease in duodenal and jejunal action potentials during fasting and with feeding, but no decreases in jejunal mucosal blood flow. The gastrointestinal myoelectrical patterns returned to those found in health on postendotoxin day 3. CONCLUSIONS: A single, sublethal dose of endotoxin results in a temporary disruption of gastrointestinal myoelectric activity similar to that seen during postoperative ileus. The etiology of this "adynamic" ileus is unknown but does not appear to be secondary to intestinal ischemia.

Action Potentials↗

The management of extrahepatic portal vein aneurysms: observe or treat?

A case of a 70 year old man who was found to have an extrahepatic portal vein aneurysm during an evaluation for hematuria is reported. Extrahepatic portal vein aneurysms are rare with only twenty cases reported in the literature. Typically, patients present with hemorrhage requiring surgical exploration or the aneurysm is discovered during evaluation of another abdominal process. Management includes careful follow-up in the asymptomatic patient without underlying liver disease or portal hypertension.

Abdominal Pain↗

Effect of endotoxin on canine gastrointestinal motility and transit.

Ileus is common during sepsis; however, the etiology of this gastrointestinal dysmotility is unclear. The aim of our study was to determine the effects of a single, sublethal dose of endotoxin on canine gastrointestinal motility, gastric emptying, gastric acid secretion, and colonic transit. Six dogs underwent placement of manometric catheters in the stomach and small bowel and insertion of a gastric and a cecal cannula. After the animals recovered, fasting and fed gastrointestinal motility was recorded, and gastric emptying and colonic transit were studied with nonabsorbable liquid and solid markers, respectively. Following completion of baseline studies, each dog was given a single dose of Escherichia coli lipopolysaccharide (200 micrograms/kg intravenously) and the studies were repeated on Postendotoxin Days 1-3. The single bolus of endotoxin abolished the migrating motor complexes, decreased the fasting motility index, decreased hydrogen ion output, slowed liquid gastric emptying, and prolonged colonic transit for 2 days. Gastrointestinal motility and transit returned to baseline on Postendotoxin Day 3. In conclusion, a single, sublethal dose of endotoxin temporarily disrupts fasting and postprandial canine gastrointestinal motility and transit.

Animals↗

Epidural analgesia shortens postoperative ileus after ileal pouch-anal canal anastomosis.

PURPOSE: A retrospective study was conducted to determine whether epidural analgesia would speed recovery from postoperative ileus in patients undergoing ileal pouch-anal canal anastomosis. METHODS: Among 85 patients who underwent proctocolectomy with ileal pouch-anal canal anastomosis at the Mayo Medical Center between January 1, 1991 and October 31, 1992, 44 were treated for postoperative pain with continuous infusion of epidural fentanyl citrate supplemented by intravenous morphine on request, while 41 controls were given only systemic morphine sulfate as needed. RESULTS: The patients in the two groups were matched and similar with regard to preoperative and operative risk factors and postoperative morbidity. No operative mortality occurred. Epidural fentanyl analgesia resulted in less need for nasogastric suction and intravenous fluids, more rapid discharge of fecal content, more rapid return to oral intake, and shorter hospitalization. CONCLUSION: Epidural analgesia with fentanyl citrate shortened postoperative ileus after proctocolectomy and ileal pouch-anal canal anastomosis.

Adolescent↗

Tonic responses of canine proximal colon: effects of eating, nutrients, and simulated diarrhea.

Our hypothesis was that the proximal colon relaxes to accommodate flow from the ileum. Therefore, we recorded tonic responses of the canine proximal colon to flow through the ileum and colon stimulated by 1) an 840-kcal meal, 2) nutrients perfused into the ileum and colon, or 3) rapid infusion of saline into the ileum with overflow into the colon. Saline infusion was considered to be a model of diarrhea, and the effects of an antidiarrheal (morphine sulfate) were therefore assessed. Proximal colonic tone was measured with a barostat. Tone increased before and after the arrival of chyme in the ileocolonic region. Perfusion of nutrients into the ileum and colon also significantly increased (P < 0.05) colonic tone compared with equal volumes of saline. Rapid perfusion of the ileocolonic segment with saline increased colonic tone; this increase was significantly greater (P < 0.01) when preceded by morphine. In contrast to our hypothesis, tone of the canine proximal colon increased in response to ileal flow. The increase in colonic tone during the late response to food was at least partly attributable to stimulation by intraluminal contents.

Animal Nutritional Physiological Phenomena↗

Ectopic jejunal pacemakers after jejunal transection and their relationship to transit.

The hypothesis was that orally moving pacesetter potentials distal to a site of jejunal transection and anastomosis would slow transit through jejunum containing them and that reoperation with excision of bowel containing these pacesetter potentials would restore transit to the control. In six conscious dogs with jejunal serosal electrodes for recording myoelectric activity and a jejunal perfusion/aspiration catheter for measuring transit, jejunal pacesetter potential frequency decreased distal to a midjejunal transection and anastomosis from 18.7 +/- 0.3 (SE) cycles/min (cpm) proximal to the site to 14.4 +/- 0.6 cpm distal to the site (P < 0.05). In addition, orally propagating pacesetter potentials occurred > 25% of the time in a 37 +/- 7 cm length of bowel distal to the site during fasting and after feeding. Transit through the segment with the orally moving pacesetter potentials was slowed during feeding (half time before and after transection, 7.7 +/- 1.1 and 13 +/- 2.0 min, respectively, P < 0.05). Resection of the segment with the abnormal pacesetter potentials shortened the length of bowel containing them to 24 +/- 2 cm (P > 0.05) and restored transit to the control. In conclusion, orally moving pacesetter potentials distal to a canine jejunal transection and anastomosis slowed transit through the segment of bowel containing them. Resection of the segment restored transit to the control.

Analysis of Variance↗

Reversal of small intestinal bypass operations and concomitant vertical banded gastroplasty: long-term outcome.

BACKGROUND: Long-term complications of jejunoileal bypass (JIB) have been reported, prompting restoration of intestinal continuity and concomitant performance of vertical banded gastroplasty (VBG) for weight control. The aim of this study was to evaluate the presentation and reversal of JIB complications, late complications, mortality, and long-term weight control in patients who have undergone JIB reversal and concomitant VBG. STUDY DESIGN: From 1981 to 1994, 37 patients were treated for complications from JIB that included diarrhea (73 percent), arthritis (46 percent), malnutrition (22 percent), urolithiasis (19 percent), electrolyte disorders (19 percent), and lack of weight loss (8 percent). Four patients required preoperative parenteral nutrition to correct protein and electrolyte imbalances. Surgical management of all 37 patients included restoration of bowel continuity and VBG during the same operative procedure. RESULTS: Postoperative complications occurred in 11 patients, including prolonged ileus in seven patients, pancreatitis in three patients, and infectious complications in two. There were no deaths. Late morbidity included staple line dehiscence in four patients, incisional hernia in three patients, and reversal of the VBG in one. All patients with diarrhea, malnutrition, electrolyte disorders, and lack of weight loss had resolution of their symptoms, while urolithiasis and arthritis resolved in 86 and 53 percent of patients, respectively. In patients available for five-year follow-up evaluation, weight changes were small, shifting from a preoperative weight of 87 +/- 19 to 90 +/- 19 kg at five years (mean +/- SD). CONCLUSIONS: Restoration of intestinal continuity combined with VBG is a safe and effective operation that will reverse most of the long-term complications of JIB and provide stable weight control for up to five years.

Acid-Base Imbalance↗