Continuous translocation of endotoxin and tumor necrosis factor translocation from the unused gut.
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Biomedical subjects
Publications and source records attributed to H R Freund.
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BACKGROUND: There is evidence that intussusception is associated with bacterial infection. It was hypothesized that a component of the bacterial wall may induce the intussusception. This study was intended to determine whether lipopolysaccharide from Escherichia coli or Salmonella can initiate intussusception in mice. METHODS: Lipopolysaccharide was injected intraperitoneally in mice, and the animals were examined for the presence of intussusception from 2 to 192 hours after injection. Gastrointestinal transit was assessed by measuring the passage of charcoal in the small intestine. Transit index was defined as the ratio between the distance traveled by charcoal and the total length of the small intestine. RESULTS: Intussusceptions were found in as much as 25.9% of lipopolysaccharide-injected animals, whereas in control animals, the incidence was zero. The threshold for the lipopolysaccharide effect was at 4 mg/kg and incidence reached a plateau at 8 mg/kg to 16 mg/kg. The incidence of intussusception peaked 6 hours after injection of lipopolysaccharide and declined to zero after 15 hours. To test the possibility that lipopolysaccharide induces intussusception by altering motility, its effect on transit index was measured. A dose of 12 mg/kg lipopolysaccharide reduced the transit index from 56.2+/-1.4% to 37.7+/-2.1% (p < 0.05). No microscopic histologic changes were found in the bowels with intussusception. CONCLUSIONS: Intraperitoneal bacterial wall lipopolysaccharide causes intussusception in mice by disturbing gastrointestinal motility.
During 1992-1996 we performed 163 laparoscopic hernia repairs in 100 men and 2 women. The mean age was 50.6; and in 61 the operation was bilateral, 66 were by transabdominal preperitoneal approach and 36 by total extra-peritoneal approach. There were only a few minor complications and total recurrence rate was only 4.3%, partly attributable to our learning curve. Laparoscopic inguinal herniorrhaphy reduces postoperative incisional and muscular pain and causes less disruption in the postoperative period than open repair. Return to normal activity and work is faster for laparoscopic than for open repair, but operating room costs are higher (time and equipment). However, economic advantages for the national economy should be considered.
We reviewed the records of 22 patients hospitalized at onset or first presentation of Crohn's disease after age 50. There were 12 females and 10 males, and the mean age was 64.5 years. The most common presenting symptoms were: abdominal pain, fever, diarrhea and weight loss. The disease was located in the small bowel in 14, in the ileo-colic region in 3 and in the colon in 5. The median interval from onset of symptoms until diagnosis was 42 months. 12 (54%) underwent surgery. All 5 patients with colonic disease were operated. 6 patients underwent small bowel resections, mostly terminal ileum, while 1 had resection of both terminal ileum and left colon. The recurrence rate was 70% in the medically treated and 50% in those operated. 1 patient died after surgery for Crohn's disease (4.5%), and 3 others died of unrelated causes. Compared to younger patients, the symptomatology, clinical course, need for and response to surgery, and its complications, did not differ in these older patients, but the recurrence rate seemed to be higher.
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.
BACKGROUND: Antireflux operations have been recommended for infants and children suffering from complications related to gastroesophageal reflux (GER). In recent years, the laparoscopic approach has been used increasingly for antireflux surgery in adult patients. This is our initial experience with Nissen fundoplication in infants and children under 2 years of age. PATIENTS: We operated on 11 patients weighing between 3.0 and 10.0 kg. The main indications for surgery were GER-induced aspiration pneumonia and failure to thrive, in spite of intensive conservative treatment. All patients except one had an associated neurological abnormality, including six patients with familial dysautonomia. RESULTS: All attempted operations were completed successfully laparoscopically, with only a few postoperative complications and acceptable short-term results. The clinical considerations and technical aspects unique to this specific group of patients are discussed. CONCLUSION: Laparoscopic Nissen fundoplication is feasible, safe, and effective, even in very small babies.
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BACKGROUND: Surgery for Crohn's disease is not intended for cure, but rather to relieve symptoms and treat complications. Perioperative morbidity, the fear of creating short bowel syndrome, and the tendency of the disease to recur convinced many physicians to refer their Crohn's patients for surgery only when life-threatening complications occur. METHODS: This is a retrospective analysis of 47 patients operated on for Crohn's disease between 1989 and 1994. Twenty-six patients were operated on for "classic" indications ("classic" group) and the other 21 were operated on to improve their quality of life ("quality" group). RESULTS: There was no operative or postoperative mortality during a mean follow-up period of 50 (27 to 84) months. All major postoperative complications occurred only in patients operated on for the classic indications (four abscesses, two fistulas, one wound dehiscence, and two small bowel obstructions). During the follow-up period, a total of 13 patients (50%) in the classic group and only 5 patients (24%) in the quality group required reintroduction of medical therapy or additional operations for exacerbations and complications of Crohn's disease. CONCLUSIONS: Our data suggest that surgical intervention intended to improve the quality of life for Crohn's disease patients is safe and effective for carefully selected patients. It does improve quality of life, may prevent life-threatening complications, and offers a lower recurrence rate following surgery.
The availability and widespread use of TPN enables physicians to help patients in a way that had not been possible in the past. However, in order to best utilize this modality, we must be aware of potential hazards and metabolic complications. Many patients receiving TPN, particularly those receiving perioperative TPN, are malnourished to various extents, and careful monitoring of glucose metabolism is warranted to avoid malnutrition-associated reactive hypoglycemia.
The appearance of focal pulmonary lesions in a patient with a nonpulmonary malignancy is worrisome. Apart from metastasis, the differential diagnosis includes benign conditions such as infectious and granulomatous diseases, enlarged lymph nodes, atelectasis, radiation pneumonitis, and bronchiolitis obliterans with organizing pneumonia (BOOP). CT-guided needle biopsy is not always diagnostic and may not be feasible in very small lesions. Since open lung biopsy is associated with considerable morbidity, many physicians tend to postpone tissue diagnosis for a few weeks and perform a biopsy only if repeat chest CT scans show increase in size or number of the lesions. This approach may lead to undesirable delay of appropriate treatment. We report video-assisted thoracoscopic lung biopsy in 7 patients with nonpulmonary malignancy who developed lung lesions following chemotherapy and/or radiation therapy. Histological examination proved metastatic lesions in only 2. There were no operative complications and recovery was rapid and smooth in all patients. Thoracoscopic lung biopsy is an effective, minimally invasive diagnostic tool that obviates the need for thoracotomy in these patients.
Short term results following laparoscopic Nissen fundoplication were evaluated in 31 patients with symptomatic gastroesophageal reflux. 6 were females and 26 males, and they ranged in age from 5 months to 64 years (mean: 4.9 years in 19 younger than 18 years, and 39.3 years in 12 adults). Most of the adults who complained of pain and heartburn underwent pH monitoring, endoscopy, and manometry as needed. Milk scan was the most useful diagnostic tool for the evaluation of the children, who suffered mainly from gastroesophageal-related pulmonary disease. Indications for laparoscopic operation were identical with those for conventional open Nissen fundoplication. 1 case of dysautonomia died postoperatively; the rate of complications, mostly minor, was 22.5%. 3 patients required conversion to open Nissen fundoplication due to cardiorespiratory instability secondary to pneumothorax in 2, and to esophageal perforation in the third. 5 adults developed temporary dysphagia. 3 children had only partial improvement in their pulmonary disease following the operation, while the other 15 had complete relief. The total time for the laparoscopic operation averaged 245 minutes in adults, and 228 in children. Discharge was usually on the fourth postoperative day in adults (mean: 6.0 days). Regurgitation and heartburn were cured in 10 out of 11 adults (91%). All parents of children were satisfied. Symptomatic outcomes following laparoscopic Nissen fundoplication compare favorably with those of open surgery with respect to mortality, complications, and outcome.
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BACKGROUND: Hyperosmotic water-soluble contrast materials have been fo und to be helpful diagnostic tools in postoperative small-bowel obstruction (POSBO); however, their therapeutic value remains controversial. PATIENTS AND METHODS: A prospective, randomized clinical study was conducted to examine the use of meglumine ioxitalamate as a supplement to the standard conservative treatment of POSBO. Patients with POSBO (n = 50) suitable for a conservative approach were randomized to receive standard conservative treatment with (n = 25) or without (n = 25) the addition of 100 mL of meglumine ioxitalamate via the nasogastric tube (patients with diffuse carcinomatosis and early POSBO were excluded). Both groups were compared for resolution of obstruction, need for surgical relief of obstruction, and complications. RESULTS: Seven (14%) patients required surgery: 3 in the contrast material group and 4 in the control group (P = not significant [NA]. Resolution of symptoms was achieved in nonsurgical patients within an average of 25.7 hours in the contrast material group and 28.7 hours in the control group (P = NS). There was no mortality in this study. In 2 (4%) patients (1 in each group), strangulated bowel was found during surgery, but only the 1 (2%) patient in the contrast material group required bowel resection. No difference was found in the length of hospital stay or rate of complications. There were no complications that could be attributed to the use of the contrast material itself. CONCLUSIONS: Although water-soluble contrast material is a safe and useful diagnostic tool, it offers no advantage as a supplement to the usual conservative treatment of POSBO.
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Splenectomy is an effective treatment for immune thrombocytopenic purpura (ITP). The recent advances in laparoscopic technique and technology have made laparoscopic splenectomy a viable option. Over 36 months we performed a total of 17 laparoscopic splenectomies, 15 of them for ITP and 2 for familial spherocytosis. We present our initial experience with laparoscopic splenectomy in 15 patients (age 16-71 years) with ITP. Operations were performed 2-24 months after the establishment of the diagnosis and initiation of appropriate therapy. Technically, the splenic artery was clipped first; the lower pole of the spleen and its posterolateral attachments were dissected using endoclips and electrocautery; the hilum and short gastric vessels were separated using an endostapler; the spleen was placed in a plastic bag, its opening pulled out through the umbilical incision, and the spleen fragmented and aspirated out of the bag. Operations lasted 100-300 min (mean 170 min). No patient required blood transfusion. The postoperative course was uneventful in all patients with minimal requirement of analgesia and early return to normal activity. Platelet counts returned to normal in all patients in a follow-up period of 2-36 months. Laparoscopic splenectomy is safe and effective for patients with ITP because of reduced operative trauma, less postoperative pain, cosmetic advantage, and possibly less postoperative complications.
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We present our initial experience with laparoscopic colonic resection in 15 patients: adenocarcinoma of the colon, 10 cases, giant villous adenoma (2), arteriovenous malformation (2), and a case of benign stricture. Mean operating time was 190 minutes and there were no intraoperative complications. The margins of resection and number of resected lymph nodes in patients with malignancy were comparable to those in the conventionally operated. Mean postoperative hospital stay was 6.1 days. During a maximum follow-up of 15 months there were no wound or trocar-site recurrences. We conclude that laparoscopic colonic resection is technically feasible and safe. However, its use for treating malignant diseases of the colon needs further study.
Splenectomy is effective in treating immune thrombocytopenic purpura (ITP). Recent advances in laparoscopic technique and technology have made laparoscopic splenectomy feasible. We performed it in 8 cases of ITP (16-34 years old, and 2-24 months after the diagnosis was made and appropriate treatment started). Indications for splenectomy were no response to corticosteroid therapy (2 patients), decrease in platelet count when attempting to taper off therapy (3), or severe side-effects of the treatment (3). 4-5 ports were used. The splenic artery was first double-clipped through an opening in the gastrocolic ligament and then the lower splenic pole and the posterolateral attachments were dissected using endoclips and electrocautery. The hilum and short gastric vessels were separated using an endostapler. The spleen was placed in a plastic bag whose open end was pulled out through an umbilical incision and the spleen fragmented and aspirated out of the bag, while it was still inside the abdomen. Blood or platelet transfusions were not needed and the postoperative course was uneventful in all, with early return to full normal activity. Postoperatively, platelets increased to more than 150,000/mm3 in all patients, and there was no further need for corticosteroids during a follow-up of 2-12 months. We recommend laparoscopic splenectomy for ITP because of the reduced operative trauma, better recovery and rehabilitation, less postoperative pain, cosmetic advantage, and possibly fewer postoperative complications.