Search PubMed⌕ Search

Biomedical subjects

H R Freund

Publications and source records attributed to H R Freund.

119 records · Page 7Linked to original sources
PubMedDate not supplied

Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide.

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.

Administration, Oral↗
PubMedDate not supplied

Antitumor necrosis factor antibodies reduce hepatic steatosis during total parenteral nutrition and bowel rest in the rat.

BACKGROUND: In previous studies, we demonstrated the overgrowth of gram-negative bacteria in the gut and an enhanced release of tumor necrosis factor (TNF) by peritoneal macrophages, suggesting that endotoxin, TNF, or both, may act as hepatotoxins to produce hepatic steatosis during total parenteral nutrition (TPN) and bowel rest. The present study attempts to better define the role of each of these two mediators. The first part examines the LD50 for various doses of endotoxin in TPN-treated rats compared with free-feeding and free-feeding saline-infused rats. In the second part we repeatedly administered anti-TNF monoclonal antibodies to rats subjected to TPN and bowel rest. METHODS: In the first set of experiments, 87 male Sabra rats were randomized into three groups: free-feeding, infused with normal saline, and infused with TPN. On day 7 of the experiment, all rats received an IV injection of endotoxin at various doses (1.5, 2.5, 5.0, 7.5, and 10 mg/kg). The LD50 in the three groups and at the various doses of lipopolysaccharide tested was determined at 24 hours postinjection. In the second set of experiments, 38 male Sabra rats were randomized into three groups: infused with normal saline and fed rat food ad libitum, infused with TPN, and infused with TPN but also receiving monoclonal antibodies against TNF. RESULTS: Lower endotoxin doses were required to achieve LD50 in the two IV-infused groups (2.5 to 5.0 mg/kg) compared with the free-feeding group (7.5 mg/kg) (p < .03). These findings suggest a moderate increase in susceptibility to the lethal effect of endotoxin in IV-treated rats. The total hepatic fat and triglyceride levels, which were markedly increased in TPN rats, were significantly reduced by using anti-TNF antibodies. Enhanced TNF production by peritoneal macrophages during TPN was completely eliminated by anti-TNF antibodies, probably the result of suppressed TNF production. CONCLUSIONS: The continuous translocation of endotoxin from gram-negative bacterial overgrowth in the gut during TPN and bowel rest results in enhanced release of TNF by macrophages. TNF causes hepatic dysfunction, portrayed in the present experimental model as hepatic steatosis. TPN-induced hepatic steatosis was significantly reduced by the administration of monoclonal antibodies against TNF-alpha.

Animals↗
PubMedDate not supplied

Pentoxifylline and thalidomide fail to reduce hepatic steatosis during total parenteral nutrition and bowel rest in the rat.

BACKGROUND: We suggested that the continuous translocation of endotoxin from Gram-negative bacterial overgrowth during bowel rest and total parenteral nutrition (TPN) causes the release of tumor necrosis factor (TNF), resulting in liver damage and hepatic dysfunction. Because TPN-induced hepatic steatosis was significantly reduced by the monoclonal antibodies against TNF, we attempted a more clinically applicable approach using pentoxifylline and thalidomide. METHODS: A control group (group I) fed rat chow and four groups of rats receiving TPN were studied. Group II received TPN only; group III, TPN and 100 mg/kg/d pentoxifylline; group IV, TPN and 200 mg/kg/d pentoxifylline; and group V, TPN and 5 mg/kg/d thalidomide. On day 7, total liver fat was determined. RESULTS: Bowel rest and TPN resulted in a significant (p < .0005) increase in liver fat content that was unaltered by either pentoxifylline or thalidomide. CONCLUSIONS: Our results show no role for pentoxifylline or thalidomide in reducing TPN-associated hepatic steatosis.

Animals↗
PubMedDate not supplied

A trend for reduced 15-day wound infection and 6 months' mortality in laparoscopic relative to open cholecystectomy: the Israeli Study of Surgical Infections.

OBJECTIVE: To utilize a naturally occurring "experiment," when introduction to laparoscopic cholecystectomy occurred in Israel; to compare the concurrent outcomes (wound infection and mortality) of laparoscopic versus open cholecystectomy; to adjust for patients' characteristics and procedural factors while making the comparisons. DESIGN: Multicenter prospective follow up, including patients' interviews prior to the operation, daily information on postoperative care, a summary of the operation report and postdischarge telephone interview 15 days after surgery. SETTINGS: A sample of 100 consecutive cholecystectomy patients from all 20 acute-care hospitals in the country, where such operations were performed. PATIENTS: 1,785 consecutive patients during 1991 and 1992; 1,184 had open cholecystectomy, and 601 had laparoscopic cholecystectomy. RESULTS: Crude wound infection rates at 15 days were 2.3% for laparoscopic cholecystectomy and 6.3% for open cholecystectomy (odds ratio [OR], 2.8; P < .001). Crude mortality rates at 6 months were 0.17% and 3.0% for laparoscopic and open procedures, respectively (OR, 18.5; P < .004). Logistic models for infection and mortality were used to adjust for case-mix and procedural factors in the comparisons between the two operations. Adjusted ORs for open versus laparoscopic cholecystectomy were 1.9 (P = .06) for wound infection and 4.3 (P = .17) for mortality. Stratification of patients on the basis of the models into high- and low-risk strata indicated that the protective effect of laparoscopic cholecystectomy was mainly evident in the high-risk group: 1.8% versus 8.3% (P < .001) for 15-day infections and 0.6% versus 4.4% (P = .017) for 6 months mortality. CONCLUSION: We conclude that, although the P values for the adjusted comparisons were of borderline significance (due to the small number of deaths in the laparoscopic group), our results suggest advantageous outcomes for laparoscopic cholecystectomy, especially among the high-risk patients.

Adult↗
PubMedDate not supplied

Abnormalities of liver function and hepatic damage associated with total parenteral nutrition.

Liver dysfunction associated with total parenteral nutrition (TPN) probably is of multifactorial etiology. Available data justify the following recommendations. First, patients should be given balanced and complete solutions tailored to their specific needs and should not be overfed. Second, serum liver enzymes should be measured at least once a week. Third, oral or enteral intake, even if minimal, should be instituted as soon as possible. Fourth, glutamine may prove useful, although this measure is experimental. Finally, if liver dysfunction is detected, oral metronidazole, neomycin, or gentamicin may prove beneficial.

Animals↗
PubMedDate not supplied

Treatment of primary and metastatic liver cancer using an implantable chemoinfusion pump.

Twenty evaluable patients with primary or secondary neoplastic liver involvement received FUDR (0.2 to 0.3 mg/kg per day) by continuous infusion to the hepatic artery for 14 days, every 4 weeks, through a surgically implanted Infusaid (USA) pump. In addition to FUDR, MMC (15 mg/m2 every 6 to 8 weeks) was given to 14 patients with colorectal cancer and one patient with breast cancer, and ADR, (40 mg/m2 every 4 to 6 weeks) was given to 5 patients with hepatocellular carcinoma. MMC and ADR were given as a bolus injection, through the pump sideport. Radiation therapy to the liver (2,000 rads in fractions of 180 to 200 rads each) was given to eight patients with colorectal carcinoma. In total, the 20 patients received 218 months of treatment and 580 injections. The overall remission rate (complete, partial and minor response) was 55%; one patient with a colorectal carcinoma achieved a CR and seven patients (35%) a PR; three patients (15%) had a MR, and in eight patients (40%) stabilization of disease was observed. Overall median survival was 12 months: 15.5 months for colorectal cancer patients and 7.5 months for patients with hepatocellular carcinoma. Toxicity consisted mainly of chemical hepatitis, mild to severe peptic disease and sclerosing cholangitis. Hematological toxicity was not observed. These data suggest that chemotherapy through the hepatic artery, while still experimental, may be considered for selected patients with tumor confined to the liver.

Adult↗
PubMedDate not supplied

A rapid and simple technique for intestinal anastomoses with a circular stapling instrument.

A recently developed stapling device (EEA, Auto Suture Co., USA), which was initially introduced for the construction of low-lying rectal anastomoses, successfully accomplished end-to-end esophagojejunostomies, end-to-side Roux-en-Y small bowel anastomoses, and end-to-end ileocolonic anastomoses. The different anastomoses were performed in five dogs; there were good results and no complications. This instrument is easy to use, saves times, and creates safe anastomoses. We suggest its wide use in gastrointestinal surgery.

Animals↗
PubMedDate not supplied

Altered gut barrier function to Candida during parenteral nutrition.

We hypothesize that catheter-related sepsis with Candida during total parenteral nutrition (TPN) is caused by Candida translocation from the gut. Fifty male Sabra rats weighing 330 +/- 40 g were randomized into four groups and put into metabolic cages: group 1 (n = 16), nonoperated free-feeding controls; group 2 (n = 10), infused with normal saline and free feeding; group 3 (n = 14), infused with TPN solution for a total of 36 kcal and 1.5 g g protein.100 g-1 body wt.day-1;group 4 (n = 10), same TPN regimen as group 3 but also receiving oral and intravenous antibiotics. On day 7, all animals received 1.5 x 10(10) viable Candida albicans CBS 562 cells by gavage, and 24 h later, the number of Candida colony-forming units in blood, mesenteric lymph nodes, and kidneys was determined. No growth of Candida was detected in group 1 or group 2. Positive Candida cultures were found in the blood, mesenteric lymph nodes, and kidneys of groups 3 and 4, although levels reached statistical significance only for mesenteric lymph nodes in group 3. Because Candida growth occurred exclusively in groups receiving TPN and bowel rest, we conclude that altered gut-barrier function to Candida occurs during TPN and speculate that Candida sepsis during TPN might be the result of Candida translocation from the gut due to the combination of high-density Candida colonization and favorable local conditions in the gut induced by TPN and bowel rest.

Animals↗