Liquid enteral diets induce bacterial translocation by increasing cecal flora without changing intestinal motility.

The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested.

Thoracoscopic surgery in a general surgical service.

Following the great success and wide acceptance of laparoscopic surgery, the mini-invasive approach has been adopted for use in thoracic surgery. Thoracoscopic surgery is gaining acceptability as the procedure of choice for the treatment of recurrent pneumothorax and bullous lung disease, peripheral benign and malignant lesions, diffuse pulmonary infiltrates, mediastinal and pleural lesions, esophageal surgery, and major pulmonary resections for primary lung tumors. We present the 4-year experience of a general surgery service that extended the use of its advanced laparoscopic skills to the performance of thoracoscopic surgery in 80 patients. Using thoracoscopy, we performed biopsy or excision of pulmonary lesions (23 patients), spontaneous pneumothorax (14 patients), thoracic sympathectomy (41 patients), and Heller's esophagomyotomy and pericardiotomy (1 patient each). The results are excellent, and we believe the procedures presented in this series, and similar ones, can be accomplished safely and successfully by well-trained laparoscopic surgeons.

A direct inhibitory effect of erythromycin on rat urinary bladder smooth muscle.

Erythromycin (EM) exerts a dual effect on the contractility of smooth muscle. An excitatory effect mediated via motilin receptors is expressed mainly in the smooth muscle of the stomach and duodenum. The other, a direct inhibitory effect mediated via an unknown mechanism, has been described in guinea-pig and human gallbladder, in the longitudinal smooth muscle of the guinea-pig small intestine and in bronchial smooth muscle. In the present study, the effect of EM on the isolated urinary bladder of the rat was examined using isometric force measurements. The muscarinic agonist carbachol evoked contractions that were reduced by EM in a concentration-dependent manner; at 5 x 10(4) M by 46% [from 1.04+/-0.42 gm. to 0.56+/-0.22 gm., (p <0.001)] and at 10(-3) M by 57% [from 1.04+/-0.42 gm. to 0.45+/-0.20 gm., (p <0.001)]. The inhibitory effect of EM was not altered by the nerve blocker tetrodotoxin. Electric field stimulation of 0.5 Hz, 1 Hz, and 2 Hz contracted the urinary bladder. Erythromycin at 5 x 10(-4) M reduced the contractions evoked at 0.5 Hz by 15% [from 0.60+/-0.22 gm. to 0.51+/-0.20 gm., (p = 0.004)] and at 10(-3) M by 23% [from 0.60+/-0.22 gm. to 0.46+/-0.12 gm., (p <0.001)]. Erythromycin failed to affect the contractions evoked by bradykinin, phenylephrine or substance P. It is concluded that EM has a direct inhibitory effect on the rat urinary bladder smooth muscle.

[Video-assisted thoracoscopic surgery for diagnosis of pulmonary lesions].

23 patients (age 11-66 years) underwent video-assisted thoracoscopic biopsy for diffuse disease or peripheral nodular lesions of the lung. 12 had been previously treated for extrapulmonary malignancy and lung biopsy was done for suspicious metastases. In all cases except 1, lesions were identified and biopsied by thoracoscopy. The postoperative course was easier and shorter as compared to thoracotomy and the mean hospital stay was only 2.5 days. Thoracoscopic lung biopsy is a safe, effective and accurate diagnostic modality for diffuse lung disease and peripheral lesions. It is associated with minimal postoperative pain and discomfort, short hospital stay, early return to normal activity, and gives good cosmetic results.

Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small intestine.

BACKGROUND: Free radicals are associated with post-ischaemic intestinal injury and contribute to major clinical problems primarily in premature infants. Various antioxidative means and modes of intervention, previously tested, have demonstrated only limited efficacy. AIMS: To study the protective activity of the stable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its respective hydroxylamine (TPL-H) against ischaemia/reperfusion (I/R) injury. METHODS: An isolated loop of ileum was created in laboratory male Sabra rats and constantly perfused with warmed normal saline. Intestinal injury was elicited through clamping of the superior mesenteric rat artery followed by reperfusion. Either TPL or TPL-H was given intravenously immediately before ischaemia or reperfusion and continuously afterwards. The rate of mucosal to lumen clearance of para-aminohippurate (PAH) was used to evaluate intestinal mucosal injury. Serum and perfusate levels of both TPL and TPL-H were measured using electron paramagnetic resonance spectrometry. RESULTS: The increase in intestinal permeability induced by I/R was significantly inhibited by both TPL and TPL-H. The nitroxide was effective also when given immediately before reperfusion. CONCLUSIONS: Through a continuous exchange, TPL and TPL-H act as self-replenishing antioxidants and thus protect from intestinal injury. This demonstrates the potential of the family of nitroxide antioxidants against oxidative stress in general and I/R injury in particular.

Plasma-to-lumen clearance of para-aminohippurate can replace 51Cr EDTA clearance in the evaluation of intestinal mucosal injury.

Intestinal mucosal injury of various degrees occurs in many clinical situations and is initially evidenced by altered mucosal permeability. The latter may be assessed in animal models by determination of plasma-to-intestinal lumen clearance of specific molecules, usually chromated 51Cr EDTA. The purpose of this study was to evaluate the usage of para-aminohippurate (PHA) as a substitute for the commonly used radioactive material, i.e., 51Cr-EDTA, in the evaluation of intestinal mucosal injury. An isolated loop of ileum was created in rats and constantly perfused with warmed normal saline. Both renal pedicles were ligated. Either 51Cr-EDTA (18.5 Bq/kg) or PAH (58 mg/kg) was injected i.v. Fifteen-minute intestinal ischemia was produced by clamping the superior mesenteric artery immediately after the end of an equilibration period. The perfusate was collected for 10 min prior to the initiation of intestinal ischemia, during the last 10 min of ischemia, and during the following three 10-min periods of reperfusion. Blood samples were collected at the end of each collection period for the determination of either PAH or 51Cr-EDTA concentrations and the calculation of either PHA or 51Cr-EDTA plasma-to-lumen clearances. PAH and 51Cr-EDTA plasma-to-lumen clearances followed the same pattern in all five assessed periods with no statistical difference between the two. PAH plasma-to-lumen clearance is a feasible, reliable, and inexpensive method for the evaluation of ischemia/reperfusion injury to the intestinal mucosa. It can safely replace the commonly used method in animal models that utilizes radioactive materials such as 51Cr-EDTA.

[Video assisted thoracoscopic surgery (VATS) for spontaneous pneumothorax].

We report our initial experience with thoracoscopic surgery in the treatment of spontaneous pneumothorax in 14 patients, mean age 30.7 years. 7 were operated following 2 episodes of spontaneous pneumothorax, 6 after their first episode, and 1 after multiple episodes. All underwent bleb resection, pleurodesis and tube thoracostomy; in 1 we converted to a limited thoracotomy (93% success rate). Only oral analgesia was required for postoperative pain control and patients were discharged 2.6 days after surgery, on average. The apparent superiority of thoracoscopic over conventional, even limited, thoracotomy seems to justify such therapy even during the first episode.

Direct inhibitory effect of erythromycin on the gallbladder muscle.

Erythromycin, a macrolide antibiotic, stimulates motor activity in various parts of the gastrointestinal tract in humans and animals. This effect of erythromycin resembles that of motilin, a gastrointestinal hormone, in evoking contractions similar to phase 3 activity of the migrating motor complex. Motilin induces contractions in the canine gallbladder but fails to evoke any response, either in vivo or in vitro, in the human gallbladder. Surprisingly, erythromycin stimulates human gallbladder emptying in healthy volunteers and in persons with diabetic autonomic neuropathy. In the present study we examined the effect of erythromycin on chemically and electrically evoked contractions of isolated gallbladders from guinea pigs and humans by use of isometric force measurements. Carbachol, a muscarinic cholinergic agonist, evoked gallbladder contractions that were diminished by erythromycin in a concentration-dependent manner: at 200 micromol/L the contractions were 86% +/- 20% of the control response, at 500 micromol/L they were 63% +/- 21% of control, and at 1000 micromol/L they were 41% +/- 20% of control (P <0.05, N = 10, mean +/- standard deviation). Electrically evoked gallbladder contractions were reduced to 68% +/- 18% of the control response with the addition of 500 micromol/L of erythromycin and to 56% +/- 19% of control after the addition of 1000 micromol/L (P <0.05, N = 8). Guinea pig but not human gallbladders contracted after stimulation with the alpha-adrenergic agonist phenylephrine. Erythromycin reduced these contractions in a concentration-dependent manner but had no effect on gallbladder contractions induced by bradykinin. In human gallbladder strips, erythromycin at 500 micromol/L reduced the contractile response to electrical stimulation to 71% +/- 16% of the control value (N = 10 [5 patients], P <0.01) and the carbachol-evoked contractions to 53% +/- 24% (P <0.01, N = 32). The inhibitory effect of erythromycin persisted in the presence of the nerve blocker tetrodotoxin at 1 micromol/L. It is concluded that erythromycin has a direct inhibitory effect on guinea pig and human gallbladder contractions.

Cooling strangulated intestine before and following release of an obstruction protects from ischemia/reperfusion injury.

OBJECTIVE: To evaluate whether cooling of ischemic intestine before and immediately after the release of the obstruction is more advantageous than is warming in an isolated ileal loop rat model. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Male Sabra rats. INTERVENTIONS: An isolated loop of ileum was created in rats and constantly perfused with warmed normal saline (37 degrees C). Intestinal ischemia was caused by clamping of the superior mesenteric artery for 15 minutes. Cooling of the isolated ileal loop to 32 degrees C by the application of cold saline was done for the last half of the ischemic period and continued during the first 10 minutes of reperfusion. The intestine was warmed to 37 degrees C for the next 20 minutes of reperfusion. MAIN OUTCOME MEASURES: The chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) plasma-to-lumen clearance rate was used for the evaluation of intestinal mucosal injury. Multiple intestinal samples were harvested at the end of the reperfusion period, and the histological features were evaluated. RESULTS: The 51Cr-EDTA plasma-to-lumen clearance rates were significantly lower (P < .001) in the rats in which cooling of the ischemic intestine was performed in comparison with the control group, indicating reduced intestinal mucosal injury in all three 10-minute reperfusion periods. Cooling also significantly changed the resultant histological damage to the intestinal mucosa exerted by ischemia (P < .001). CONCLUSION: Cooling of the ischemic intestine before the release of the obstruction and for a short period during reperfusion provides significant protection from ischemia/ reperfusion injury compared with the traditional method of warming the ischemic intestine.

The contribution of inflammatory mediators and nitric oxide to lipopolysaccharide-induced intussusception in mice.

Intussusception is a major cause for intestinal obstruction in children. Its etiology is unclear, but it is often associated with some kind of infection. We have developed a model for intussusception in mice using intraperitoneal (IP) injection of lipopolysaccharide (LPS). The objective of this study was to identify the putative mediators that participate in this LPS-induced intussusception. LPS (12 mg/kg) was injected into adult mice (N = 52) and 6 hr later, 25% of the animals demonstrated intussusception in the small or large intestine. We next tested whether nitric oxide (NO) or various inflammatory mediators contributed to this effect: Indomethacin (10 mg/kg) injected with LPS (12 mg/kg) completely prevented the effect of LPS (N = 20). The tumor necrosis factor (TNF) blocker pentoxifylline (200 mg/kg) significantly reduced the incidence of intussusception to 6.6% (N = 30). The platelet-activating factor (PAF) antagonist BN52021 (10 and 20 mg/kg) reduced the incidence of intussusception to 13.3% in both doses (N = 15 for each dose). Addition of 2% arginine (NO precursor) to the drinking water 36 hr before the injection of LPS increased the incidence of intussusception to 30.7% (N = 32). In mice injected with the NO synthase inhibitor L-NAME (20 mg/kg) only 3.8% developed intussusception (N = 26). Our results indicate that the induction of intussusception by LPS proceeds via parallel pathways involving cytokines, prostaglandins, and NO. Our previous pathological study showed that LPS did not cause any changes that may act as a lead point for the intussusception, suggesting that LPS induced intussusception by altering gut motility. We therefore propose that these mediators combine to induce disturbed gut motility that results in the formation of intussusception.

Pentoxifylline attenuates ischemia/reperfusion injury to the small intestine in the rat.

There is a large body of evidence that neutrophils may play an important role in the mucosal injury that follows ischemia of the intestine. Pentoxifylline (PTF), a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and restores intestinal blood flow following hemorrhagic shock and sepsis. The purpose of this study was to evaluate the protective properties of PTF in an ischemia-reperfusion model of the intestine and whether its action is mediated through tissue neutrophils as assessed by myeloperoxidase (MPO) determination. Intestinal ischemia of either 1 or 2 h was induced in rats by clamping the superior mesenteric artery, followed by a 17-min reperfusion period. PTF (25 mg/kg) or saline solution was injected IP 10 min prior to ischemia. Multiple bowel samples were harvested at the end of the reperfusion period and evaluated for histology and tissue MPO. PTF significantly changed the resultant histologic damage to the intestinal mucosa exerted by prolonged ischemia of 1 and 2 h duration, although the beneficial effect of PTF in this animal model was independent of the number of tissue neutrophils as assessed by tissue MPO levels. Pretreatment with PTF can thus reduce the histologic damage caused by prolonged ischemia to the intestine.

Caco-2 and IEC-18 intestinal epithelial cells exert bactericidal activity through an oxidant-dependent pathway.

Intestinal epithelial cells have receptors that recognize bacterial antigens and in some circumstances are actively involved in bacterial internalization. To test the hypothesis that intestinal epithelial cells possess bactericidal capabilities, the bactericidal activity of two intestinal cell lines (IEC-18 and Caco-2) was measured using Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli as test organisms. The relative bactericidal efficacy of these two intestinal cell lines to kill these bacteria was compared against neutrophils (PMN) using a standard in vitro bactericidal assay. The IEC-18 and Caco-2 cells as well as the PMNs killed S. aureus and P. aeruginosa but not E. coli (p < .05). In fact, when tested in serum-free medium, the IEC-18 and Caco-2 cells killed a greater percentage of bacteria than the PMNs (p < .05). The addition of the antioxidant, superoxide dismutase, significantly reversed the bactericidal activity of both Caco-2 cells and neutrophils for P. aeruginosa and S. aureus, while catalase had no effect. Nitric oxide inhibition by NG-nitro-L-arginine methyl ester (L-NAME) had no effect on bactericidal activity of Caco-2 cells. These results indicate that intestinal epithelial cells can kill certain strains of bacteria and may function as "nonprofessional" phagocytes. Additionally, the mechanisms involved in the killing of P. aeruginosa and S. aureus by the Caco-2 and IEC-18 cells appear similar to the PMNs to the extent that bactericidal activity appeared to be oxidant-mediated but not nitric oxide-mediated in both the Caco-2 cell line and in the neutrophils.

Postischemic intestinal motility in rat is inversely correlated to length of ischemia. An in vivo animal model.

An inverse correlation between postischemic gastrointestinal motility and the length of intestinal ischemia was found in an animal model. Intestinal ischemia was caused without concurrent laparotomy and for a predetermined time period (ischemia time) by pulling on an external nylon thread that was threaded through a double-lumen catheter. This catheter was passed into the abdominal cavity to encircle the superior mesenteric artery. Gastrointestinal motility was determined by the introduction of a color-marked meal into the animal's stomach and the measurement of the proportionate length of the small bowel filled with it (transit index). This simple and reliable animal model can also be used for the evaluation of techniques and pharmacological manipulations aimed at modulation of the effects of intestinal ischemia on intestinal motility and its consequences.

Inhibition of gastrointestinal motility by MPTP via adrenergic and dopaminergic mechanisms.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in mice and caused an acute inhibition (of over 60%) of gastrointestinal motility, which was measured by the transit of charcoal. This inhibition was not related to conversion of MPTP to MPP+. Administration of the beta-adrenergic blocker propranolol significantly reduced, but did not completely block, the effect of MPTP. The dopaminergic blocker haloperidol also partly reversed the effects of MPTP. When these blockers were administered together, the action of MPTP was fully blocked. The results indicate that the toxin acted by releasing catecholamines (presumably norepinephrine and dopamine), thereby inhibiting motility.

Epidural anesthesia accelerates the recovery of postischemic bowel motility in the rat.

BACKGROUND: Intestinal ischemia is associated with derangement of gastrointestinal motility. Uncontrolled clinical observations that bupivacaine injected into the epidural space causes faster recovery of bowel motility after various abdominal operations led us to assess the hypothesis that epidural anesthesia can hasten the recovery of gastrointestinal motility in the immediate postischemic period. METHODS: Gut motility studies were performed in rats in which epidural anesthesia and intestinal ischemia could be initiated without the need to provoke surgical trauma. Epidural lidocaine was compared to epidural saline in their effect on intestinal motility after a 30-min period of bowel ischemia. RESULTS: Total ischemia to the small bowel resulted in pronounced postischemic adynamic ileus as evidenced by only 0.7% of the total length of the small bowel filled with a marker meal at the end of the study period (transit index) compared with 84.4% in the control group. Lidocaine epidural anesthesia caused significantly more rapid resolution of the adynamic ileus (60.3% of the bowel filled with the marker meal vs. 30.9% in the controls in which saline was injected). CONCLUSIONS: Epidural lidocaine compared to epidural saline hastens the recovery of gastrointestinal motility in rats after a 30-min period of bowel ischemia. This effect may be elicited by attenuation of sympathetic efferent inhibitory pathways or by vasodilatation caused by the sympathetic block. These results suggest that lidocaine epidural block not only alleviates pain in situations of ischemic injury to the bowel but may also hasten the recovery from postischemic paralytic ileus.

The time sequence of injury and recovery following transient reversible intestinal ischemia.

Intestinal mucosal damage and regeneration were examined in rats following transient ischemia produced by the occlusion of the superior mesenteric artery for 30 min. Animal groups were assigned for harvesting of small bowel specimens at 10, 17, and 30 min and 1, 2, 3, 4, 6, 12, and 24 hr post-relief of ischemia. Severe damage to the villi was evident already at 10 min postischemia. Thereafter a very rapid restitutional process was observed with restoration of villi epithelium in 47.6% of the examined animals at 60 min, 75% at 4 hr, and 100% at 12 hr. This rapid sequence of events should be taken into consideration when designing experimental ischemic bowel animal models and possible therapeutic modalities.

The modulatory role of gut hormones in elemental diet and intravenous total parenteral nutrition-induced bacterial translocation in rats.

We have previously shown that parenteral and certain elemental diets promote bacterial translocation and that this diet-induced bacterial translocation can be prevented by the provision of bulk-forming dietary fiber. The goal of the current study was to test the hypothesis that fiber's protective effect on diet-induced bacterial translocation was mediated by trophic gut hormones. This hypothesis was tested by using bombesin (which stimulates gut hormone release) or the somatostatin analog Sandostatin (which inhibits gut hormone release) to modulate gut hormone release in rats receiving rat food, intravenous total parenteral nutrition, or an elemental diet. Both bombesin and fiber were effective in preventing elemental diet-induced bacterial translocation, whereas octreotide acetate abrogated the protective effect of fiber. Bombesin was also effective in limiting bacterial translocation in parenterally fed rats. Although both enteral (elemental diet) and parenteral diet-induced bacterial translocation were associated with cecal bacterial overgrowth, loss of small-bowel weight, and loss of mucosal protein content, none of these factors seemed to be primarily responsible for bacterial translocation. Because bombesin decreased the incidence of villous injury in the elemental diet-fed rats and decreased the incidence of villous injury and prevented loss of intestinal barrier function to horseradish peroxidase in the parenterally fed rats, it is possible that bombesin exerted its protective effect by limiting mucosal injury and preserving barrier function.

Bombesin protects against bacterial translocation induced by three commercially available liquid enteral diets: a prospective, randomized, multigroup trial.

OBJECTIVE: To test the hypothesis that certain commercially available liquid diets would cause bacterial translocation and that this diet-induced translocation could be reduced with bombesin (an intestinal hormone stimulant). DESIGN: Prospective, multigroup trial in which animals fed each test diet were randomized to receive either bombesin or saline for 7 days. On day 7, the mice were killed and their organs were cultured for translocating bacteria, their cecal bacterial population concentrations were measured, and ileal and jejunal mucosal protein content was determined. SETTING: Small animal laboratory. SUBJECTS: Outbred ICR mice weighing 25 to 35 g. INTERVENTIONS: Mice received bombesin (10 micrograms/kg) or saline subcutaneously three times daily for 7 days before sacrifice. MEASUREMENTS AND MAIN RESULTS: The incidence of bacterial translocation to the mesenteric lymph node was significantly increased (p < .05) in mice fed Vivonex (53%), Criticare (67%), or Ensure (60%) compared with chow-fed controls (0%). All three liquid diets were associated with the development of cecal bacterial overgrowth and loss of jejunal and ileal mucosal protein content. Bombesin reduced the incidence of bacterial translocation and loss of mucosal protein content in all three liquid diet groups (p < .05), but did not prevent diet-induced cecal bacterial overgrowth. CONCLUSIONS: Three different liquid diets induced bacterial translocation to the mesenteric lymph node. Since bombesin was effective in reducing bacterial translocation, it appears that bacterial translocation induced by these liquid diets can be modulated hormonally.

Spontaneous rupture of the urinary bladder complicated by extensive fascitis: the importance of a high index of suspicion.

Spontaneous rupture of the urinary bladder is a rare entity. This is, in part, the cause for the low rate of correct preoperative diagnosis, the high rate of delayed diagnosis, morbidity and mortality. We report a case of spontaneous rupture of the urinary bladder in an adult patient, complicated by extensive fascitis of the abdominal wall. The stormy course and long hospitalization in the case described are characteristic of patients with spontaneous bladder rupture and warrant a high index of suspicion in order to achieve an early diagnosis.