Search PubMed⌕ Search

Biomedical subjects

O D Rotstein

Publications and source records attributed to O D Rotstein.

162 records · Page 9Linked to original sources

Fibrin in peritonitis. V. Fibrin inhibits phagocytic killing of Escherichia coli by human polymorphonuclear leukocytes.

Fibrin deposition initiated by peritonitis is thought to be an important local defense mechanism because it sequesters and walls off bacterial spillage. However, fibrin has been shown to predispose to residual abscess formation in rat peritonitis model. To examine the potential mechanisms of this effect, fibrin was tested in vitro for its inhibitory effect on neutrophil function. At all concentrations tested (50-1000 mg/dl), fibrin significantly impaired the ability of neutrophils to kill Escherichia coli. This inhibition occurred in a dose dependent fashion with almost complete prevention of killing at the highest concentration tested. Further studies showed that pre-exposure to fibrin did not reduce the neutrophil's ability to degranulate, undergo a respiratory burst, or kill E. coli, indicating that fibrin did not cause irreversible damage to the normal microbicidal functions of the neutrophil. However, fibrin, at physiologic concentrations, significantly impaired phagocytosis of radiolabeled E. coli. The data support the concept that phagocytosis of bacteria is impaired by neutrophils enmeshed in fibrin. Thus, contaminated fibrin could act as a nidus for residual abscesses formation following peritonitis even if an adequate number of normal leukocytes were present.

Escherichia coli↗

Microbiologic features and treatment of persistent peritonitis in patients in the intensive care unit.

The charts of 25 patients who died in the intensive care unit of persistent peritonitis after abdominal operations were reviewed to determine the microbial flora and the efficacy of antibiotic treatment. All patients had undergone two or more surgical procedures for abdominal sepsis and 23 had at least three-system organ failure. The most common organisms cultured were: Staphylococcus epidermidis, 24 cultures from 16 patients, Candida albicans, 19 cultures from 10 patients, Pseudomonas aeruginosa, 16 cultures from 12 patients, Enterobacter, 16 cultures from 8 patients and enterococcus, 14 cultures from 8 patients. The classic isolates, Escherichia coli (11 cultures from six patients) and Bacteroides fragilis (4 cultures from three patients) were found infrequently. To determine the adequacy of antimicrobial therapy for this "new" flora, we examined the ability of appropriate agents to eradicate the micro-organism upon subsequent culture. Candida sp. were eradicated in 54% (6 of 11) of the assessable cases, while enterococcus and S. epidermidis were cleared in only 25% and 28% respectively. The spectrum of intra-abdominal organisms cultured from critically ill surgical patients in the intensive care unit differs from that seen in those with acute peritonitis. Despite administration of appropriate antimicrobial agents, these organisms tend to persist, probably reflecting impaired host defences with multiple-system organ failure rather than antimicrobial failure.

Adult↗

Gastrointestinal phytobezoars: presentation and management.

A chart review from 1975 to 1985 at the Toronto Western Hospital identified 16 patients (9 women and 7 men, between the ages of 39 and 83 years) with gastrointestinal phytobezoars. Nine had previously undergone vagotomy and drainage procedures. There were two distinct clinical groups, dependent on the location gastric bezoars presented with chronic burning epigastric pain and nausea and vomiting in addition to anorexia and weight loss. Six of seven patients with small-bowel bezoars had acute small-bowel obstruction, manifested by crampy abdominal pain, vomiting and obstipation. In the seventh patient the bezoar was found incidentally in an efferent loop during endoscopy. Gastric bezoars were all diagnosed by endoscopy; patients with small-bowel bezoars had x-ray films compatible with small-bowel obstruction. The obstructing small-bowel bezoars were found at midileum and proximal jejunum. Five patients underwent proximal enterotomy with bezoar removal; in one the bezoar was milked distally into the cecum. One patient also had multiple nonobstructing small-bowel bezoars removed through the single enterotomy and another had a separate gastrotomy for removal of a gastric bezoar. The postoperative courses were uncomplicated except for wound infection in one patient. None of the patients with an isolated gastric bezoar required surgery. Three patients were successfully treated with gastric lavage and the others with clear fluid diet.

Adult↗

Mediastinitis after whiplash injury.

The authors describe a rare complication of whiplash injury. Diffuse mediastinitis resulted from extension of a whiplash-induced retropharyngeal abscess into the thorax. Early diagnosis of the cervical infection was masked by the simultaneous presence of infectious mononucleosis. Aggressive surgical management including bilateral thoracotomy was required to resolve the septic course. A review of the literature discusses the pathogenesis of this complication including the route of extension into the mediastinum and supports the use of aggressive surgical therapy to reduce the associated mortality.

Adult↗

Lethal microbial synergism in intra-abdominal infections. Escherichia coli and Bacteroides fragilis.

The ability of Bacteroides fragilis and Escherichia coli to produce synergistic mortality when mixed into intraperitoneal (IP) fibrin clots was tested in rats. The addition of B fragilis (2 X 10(9) colony-forming units/clot) to E coli (2 X 10(8) colony-forming units/clot) in the clot significantly enhanced both early and late mortality rates when compared to either E coli or B fragilis alone. Multiple washings of B fragilis prior to mixing with E coli in the clot delayed the enhancement of lethality from 24 to 48 hours. By seven days, washed B fragilis was as synergistic with E coli as unwashed B fragilis plus E coli. Furthermore, unwashed killed B fragilis was as synergistic when mixed with E coli in the fibrin clot as unwashed living B fragilis. However, washed dead B fragilis plus E coli produced no greater mortality than E coli alone. The lethality of an IP clot containing E coli was significantly increased when B fragilis was mixed with it in the same clot, injected free IP, and or implanted into a separate IP clot. Intraperitoneal E coli-fibrin clot lethality was not increased by subcutaneous B fragilis and was only slightly enhanced by intravenous B fragilis inoculation. The strain of B fragilis used in these studies did not produce fibrinolysins at any concentration. The data support the idea that synergistic mortality between E coli and B fragilis in this model is caused by a heat-stable surface factor produced by B fragilis, which acts to increase the lethal effects of E coli.

Abscess↗

Gastropleural fistula. Report of three cases and review of the literature.

Three cases of gastropleural fistulas of different causes are presented. Patients with acute fistulas from ruptured intrathoracic portions of stomach appear to benefit from early surgery and repair. The management of more insidious gastropleural fistulas probably demands a more conservative approach.

Adult↗

In-vivo bactericidal activity of Sch 34343 in Bacteroides fragilis abscesses and in Bacteroides fragilis-Escherichia coli abscesses.

Bacteroides fragilis pure-culture abscesses and Bact. fragilis-Escherichia coli mixed-culture abscesses were initiated subcutaneously in mice and intraperitoneally in rats. Within 1 h after injection of Sch 34343, the drug was present in higher concentrations in the abscesses than in the blood of infected animals. After five days of Sch 34343 therapy with either 100 or 400 mg/kg administered five times a day to mice with subcutaneous abscesses, the numbers of Bact. fragilis in pus decreased approximately three log-fold, reflecting a killing of 99.99% of the viable Bact. fragilis, while the numbers of E. coli decreased approximately 0.5 log-fold, reflecting a killing of 50% of the viable E. coli. After five days of therapy with either 50 or 150 mg/kg administered five times a day to rats with intraperitoneal fibrin clot abscesses, the viable Bact. fragilis again decreased three log-fold; the viable E. coli decreased one log-fold in rats given the higher dosages of the drug. Sch 34343 is a promising agent for the treatment of anaerobic infections because it can penetrate into anaerobic abscesses and can kill large numbers of bacteria within abscesses.

Abscess↗

Succinic acid, a metabolic by-product of Bacteroides species, inhibits polymorphonuclear leukocyte function.

Anaerobes, in particular Bacteroides spp., are the predominant bacteria present in mixed intra-abdominal infections, yet their critical importance in the pathogenicity of these infections is not clearly defined. Succinic acid, a major fatty acid by-product of Bacteroides metabolism, was tested for its effect on neutrophil function to determine whether it might play a role in enhancing the virulence of Bacteroides-containing infections. At pH 5.5 but not pH 7.0, succinic acid at concentrations commonly found in clinical abscesses profoundly inhibits in vitro neutrophil function. It virtually obliterates phagocytic killing of Escherichia coli and reduces neutrophil random migration and chemotactic response to formyl-methionyl-leucyl-phenylalanine and C5a. These effects occur in conjunction with a reduced chemiluminescent peak and delayed time to the peak. The effect on neutrophils is only partially reversible by multiple washings. These findings suggest that succinic acid may be an important Bacteroides virulence factor when present in the microenvironment of a mixed intra-abdominal infection in which concentrations are high and the pH of the medium is reduced.

Bacteroides↗

Mechanism of the adjuvant effect of hemoglobin in experimental peritonitis. IX: The infection-potentiating effect of hemoglobin in Escherichia coli peritonitis is strain specific.

Hemoglobin solutions have been said to consistently increase the lethality of otherwise nonlethal bacterial inocula in experimental models of Escherichia coli peritonitis. We tested the capacity of stroma-free hemoglobin to potentiate the lethality of each of 26 separate clinical isolates of E. coli. The LD50 of each strain with and without stroma-free hemoglobin was then correlated with the ability of that strain to express putative "virulence characteristics": the expression of 0 (lipopolysaccharide) and K (capsular) antigens, the ability to produce colicin V, the capacity to hemagglutinate mammalian red cells in the presence of 1% mannose, and the ability to secrete alpha-hemolysin. No perfect correlations were found. The LD50 of only four of the 26 strains of E. coli was affected by hemoglobin. Each of these four strains could hemagglutinate red cells and secreted alpha-hemolysin. Many other strains whose lethality was not increased by hemoglobin also had these virulence properties. We must conclude that the infection-potentiating effect of hemoglobin cannot be shown for most clinical isolates of E. coli and that the mechanism cannot be correlated with the usual "virulence characteristics" of E. coli.

Adhesiveness↗

Fibrin in peritonitis. IV. Synergistic intraperitoneal infection caused by Escherichia coli and Bacteroides fragilis within fibrin clots.

We measured the rate of lethality and abscess formation in rats that underwent intraperitoneal implantation of fibrin clots contaminated with either Escherichia coli or Bacteroides fragilis alone or in combination, to determine whether the two organisms together would produce a synergistic infection. Ten-day mortality produced by 10(9) colony-forming units (CFU) of E coli was 33.3%. Encapsulated B fragilis led to 3.3% mortality. Escherichia coli (5 X 10(8) CFU) plus B fragilis (5 X 10(8) CFU) led to a sharp increase both in the rate and final ten-day mortality (80.0%). Eighty percent of the rats that received E coli (10(9) CFU within fibrin clots) had abscesses determined on the basis of grossly purulent material. All animals that received B fragilis and survived ten days contained abscesses. Synergy between E coli and B fragilis was noted to occur only when 5 X 10(8) CFU of each organism was present within the fibrin clot. Lower numbers did not produce significant synergy compared with controls that received either E coli or B fragilis. Quantitation of the number of organisms present at 24 hours within contaminated fibrin clots demonstrated a similar amount of growth of both organisms, either when added alone or in combination as copathogens.

Abscess↗

Percutaneous aspiration and drainage for suspected abdominal infection.

Percutaneous drainage (PCD) of abdominal infection is a therapeutic modality whose role is not well defined. Surgical literature on abdominal infection cites a cumulative mortality rate in the range of 20% to 30%, markedly dissimilar from the 80% to 90% cure rates reported in the literature on PCD. We reviewed the PCD experience at a tertiary teaching hospital from 1981 to 1983. Fifty-five patients were suspected to have localized abdominal infection and underwent 66 procedures. PCD was attempted after percutaneous needle aspiration produced drainable fluid. Cure is defined by complete resolution of the abdominal process without any surgical intervention. Palliation is defined as acute decompression of the abdominal process permitting an elective corrective procedure to be performed. Failure is defined as false diagnosis, unsuccessful drainage requiring operation, or recurrence of infection. Diagnosis of the abdominal process was successfully made by aspiration in 59/66 (89%) attempts. PCD was curative in 31/66 (47%) attempts and failed or was palliative in 35/66 (53%). Simple nonfungal, nonfistulous abdominal abscesses were cured with PCD in 25/26 attempts (96%). PCD failure was encountered in 10 infected organized hematomas or thick phlegmons, nine fungal infections, nine abscesses with enteric communication, and five infected necrotic tumors. Abscesses with an underlying enteric communication were cured in 28%, were palliated in 32% and failed in 32% of PCD attempts. Abscesses with yeast as a major component or with necrotic tumor were never cured with PCD. PCD is a valuable diagnostic and therapeutic tool that is curative in simple abdominal abscesses. Its therapeutic role in complex abdominal infections seems to be limited.

Abdomen↗

Mechanism of the adjuvant effect of hemoglobin in experimental peritonitis: VIII. A leukotoxin is produced by Escherichia coli metabolism in hemoglobin.

Hemoglobin, but not albumin, has long been recognized as an infection potentiating factor in experimental Escherichia coli peritonitis, but the mechanism has defied definition. We have shown previously that stroma-free hemoglobin is not toxic to polymorphonuclear neutrophils. To test the hypothesis that hemoglobin provides a nutritional boost to the growth of E. coli in vivo, we inoculated E. coli into dialysis bags containing equivalent amounts of stroma-free hemoglobin or albumin. These bags were implanted into the peritoneal cavity of rats and at intervals the fluid was removed and the bacteria enumerated. This technique allows for intraperitoneal bacterial growth but eliminates the variables of lymphatic clearance and phagocytic ingestion. The growth rate of E. coli was the same irrespective of the nutritional supplement in the bag. Thus there is no experimental support for the notion that hemoglobin directly accelerates E. coli proliferation under in vivo conditions. To test the hypothesis that a leukocyte toxin may result from E. coli growth in hemoglobin, we exposed normal human neutrophils to the sterilized contents of the peritoneal dialysis bags. In vitro function of the neutrophils (viability, random migration, chemotaxis, phagocytosis, bacterial killing, and chemiluminescence) was significantly depressed by prior exposure to hemoglobin supernatants that had supported E. coli proliferation in vivo. Stroma-free hemoglobin had minimal adverse effects. Albumin supernatants that had supported E. coli proliferation in vivo had significantly less effect on neutrophil function even though the endotoxin levels were identical to the hemoglobin E. coli solutions. We must conclude that leukotoxins result from E. coli growth in solutions of pure hemoglobin. The data support the idea that the infection potentiating effect of hemoglobin in vivo is due to such leukotoxins.

Animals↗

Sustained alterations in lipoprotein cholesterol concentrations dependent on the daily distribution of lipid intake.

Since the fat content of a single meal influences chylomicron size and hence intestinal apoprotein synthesis, we determined the chronic effects of the daily distribution of fat intake on plasma concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Eight normal male subjects ingested 100 g of fat (a) as a bolus at the evening meal (SL) or (b) equally distributed over 4 meals (q4h) (DL). Each diet was consumed for 7 days; studies were performed 14 days apart using a crossover design and paired comparisons. Nutrient intake and body weight were held constant. At the end of the DL dietary regimen, fasting plasma concentrations of TC, LDL-C and HDL-C were significantly increased as compared to the SL phase of study (TC: 174 +/- 2.9 (mean +/- SEM) vs 161 +/- 2.7; LDL-C: 108 +/- 3.2 vs 98 +/- 3.3 and HDL-C: 53 +/- 1.1 vs 48 +/- 0.8) (P less than 0.05). The consumption of 100 g/day of fat in several small meals results in a sustained increase in LDL-C and HDL-C. This may be due to increased synthesis of lipoprotein components (e.g. apoprotein A-I) or to altered metabolism of intestinal and hepatic TG-rich lipoproteins dependent on size, number and apoprotein composition.

Adult↗

Prevention of cholesterol gallstones by lignin and lactulose in the hamster.

The effect on prevention of cholesterol gallstones by a nonfermentable type of fiber, lignin, and a fermentable fiber analogue, lactulose, was studied in hamsters fed an essential fatty acid deficient diet. Control animals had a high incidence of cholesterol gallstones (21 of 24) and lithogenic bile (lithogenic index 1.08). Animals fed lignin had significantly fewer gallstones (11 of 25), improved cholesterol saturation of gallbladder bile, and increased fecal bile acid excretion. Lactulose-fed animals had significantly fewer gallstones (12 of 24) but no significant change in cholesterol saturation of gallbladder bile or in fecal bile acid excretion. Serum cholesterol concentration was reduced, however, and fecal neutral steroid excretion was increased. Gallstones were completely prevented in animals fed both lignin and lactulose (0 of 22), but gallbladder bile cholesterol saturation was not significantly different from the lignin-fed group. Gallbladder bile mucopolysaccharide concentrations did not differ among groups. Lignin appears to prevent cholesterol gallstones in this model by improving cholesterol saturation of bile. The mechanism of action of lactulose is not yet clear.

Animals↗

Diagnostic and therapeutic challenges of intraabdominal infections.

With the advances that are being made in many areas of medicine, the surgeon must be familiar with infectious diseases of the peritoneal cavity, which have increased in scope and complexity. In addition to the surgical management of secondary peritonitis resulting from perforation of the gastrointestinal tract, the practicing surgeon may be called on to manage patients with cirrhosis with infected ascitic fluid as well as patients undergoing peritoneal dialysis with infected dialysis fluid. In addition, there is increasing recognition of a group of patients with persistent intraabdominal sepsis or tertiary peritonitis in whom infection is associated with multiple systems organ failure and general depression of the immune system. This article endeavors to present an overview of the diagnostic and therapeutic approaches to these disease entities.

Abscess↗

Mechanisms of microbial synergy in polymicrobial surgical infections.

Surgical infections are almost always polymicrobial, yet the critical importance of bacterial mixtures in these infections has received relatively little attention. The convincing data on the prevalence of mixed infections in surgery are reviewed. Both clinical and experimental evidence indicate that true synergy between certain aerobes and anaerobes may exist. Of the possible mechanisms of synergy, the most important seems to be the ability of anaerobes, their metabolic products, or their capsules to inhibit phagocytosis of aerobes by leukocytes. Other mechanisms of importance in special microbial combinations include provision of essential nutrients such as vitamin K, succinate, and various growth factors by one microbe to the other; alteration of local environment, including reduction of the oxygen tension and lowering of redox potential; and the provision of substances toxic to the host that permit species of bacteria to flourish concurrently. Further study of these interactions will shed light on the causes and correction of treatment failure.

Abdomen↗