Search PubMed⌕ Search

Biomedical subjects

R M Condie

Publications and source records attributed to R M Condie.

At least 37 records · Page 2Linked to original sources
PubMed1988

Hemoglobin: a lifesaver and an oxidant. How to tip the balance.

Hemoglobin solutions were assessed in terms of their ability to promote lipid peroxidation, which was quantitated by measuring the formation of thiobarbituric acid reactive substances (TBARS) under specified conditions in murine brain homogenates. Solutions designed for use in acute treatment of hypovolemic shock and trauma should incorporate ingredients specifically aimed at decreasing oxygen and lipid radical mediated injury occurring secondary to ischemia and reperfusion. A number of strategies aimed at decreasing the oxidant effect of hemoglobin solutions and other blood and plasma substitutes have been evaluated. These include use of the naturally occurring anti-oxidants in human plasma, specifically transferrin and ceruloplasmin. Similarly, certain iron chelators, such as deferoxamine (Desferal, Ciba-Geigy), effectively prevent molecular and cellular damage caused by iron catalyzed formation of oxygen derived radicals.

Animals↗
PubMed1987

The use of allogeneic stimulation and exogenous interleukin for syngeneic tumor rejection.

Increased survival in the syngeneic tumor-challenged host was accomplished by the addition of exogenous IL-2 with syngeneic tumor and by simultaneous administration of allogeneic plus syngeneic tumor cells. Whether the mechanisms responsible for this increased longevity are due to the same type of modulation of the immune system is undetermined. These results, however, suggest a therapeutic method of manipulating tumor and IL administration to trigger a sluggish or nonreactive immune system to respond in situations in which it otherwise would not be programmed to react.

Animals↗
PubMed1984

Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomegalovirus globulin. Randomized trial in bone marrow transplant recipients.

We have completed a randomized trial to evaluate the safety and effectiveness of hyperimmune cytomegalovirus intravenous human globulin in prevention of cytomegalovirus infection and related problems in bone marrow transplant recipients. Prophylactic intravenous administration of this native, intact, hyperimmune, cytomegalovirus IgG, at a dose of 200 mg/kg 25, 50, and 75 days following transplant resulted in complete protection against cytomegalovirus infection during the 120 days covered by the treatment (p = 0.009). There was no interstitial pneumonia or mortality in the group receiving the hyperimmune IgG. This is significant at the p = 0.014 when compared with the supporting treatment control group. In bone marrow transplant recipients, prophylaxis with a total dosage of 0.6 g/kg of an intravenous hyperimmune cytomegalovirus globulin was safe and afforded effective protection against cytomegalovirus infection and interstitial pneumonia in this high-risk population.

Adolescent↗
PubMed1984

Anticore endotoxin F(ab')2 equine immunoglobulin fragments protect against lethal effects of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis and shock remain a cause of substantial morbidity and mortality in hospitalized patients despite appropriate antimicrobial therapy, fluid resuscitation, and monitoring. We sought to test the ability of equine antibody directed against core endotoxin, a portion of bacterial outer membrane lipopolysaccharide common to many gram-negative microorganisms, to bind to various gram-negative bacteria in vitro, to promote bacterial phagocytosis by leukocytes, and to protect against lethal gram-negative bacteremia in mice. The importance of the IgG Fc leukocyte attachment site was examined by comparing the ability of intact IgG and IgG F(ab')2 fragments to protect against lethality during murine sepsis. A single horse was immunized with Escherichia coli J5, an organism that expresses a portion of core endotoxin extensively on the cell surface. Preimmunization IgG and F(ab')2 possessed no titer as determined by enzyme-linked immunosorbent assay, did not promote in vitro phagocytosis, and did not protect in vivo. Postimmunization IgG and F(ab')2 possessed a significant titer to E. coli J5 whole cell and lipopolysaccharide antigens and provided significant (p less than 0.05) protection in vivo during lethal intravenous sepsis caused by either E. coli J5, E. coli 0111:B4, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Only postimmunization IgG, but not F(ab')2, promoted in vitro phagocytosis of these same organisms. We therefore hypothesized that protection occurred as a result of antitoxin activity rather than opsonization and phagocytosis, as F(ab')2 fragments were as active as the intact molecule. Further studies must be done to determine the role of anticore endotoxin antibody in conjunction with antibiotics so that appropriate clinical studies may be undertaken.

Animals↗
PubMed1983

Antithymocyte globulin treatment of severe aplastic anaemia.

Nineteen patients with severe aplastic anaemia were treated with antithymocyte globulin. Ten patients obtained remissions (transfusion independent, at least 45000 platelets and 2000 PMN/mm3) within 2-3 months and continue in remission 5-35 months after antithymocyte globulin. Ages of responders ranged from 17 to 71. Complications of antithymocyte globulin included arthralgias, rash, serum sickness, angioedema and fever. Two patients died during, two shortly after, and one 10 months after therapy. One patient with a previous remission following antithymocyte globulin relapsed and achieved a second remission with retreatment. Previous androgen therapy did not affect outcome since two of four patients with and eight of 15 patients without previous androgen therapy achieved remission with ATG. Treatment with antithymocyte globulin is a promising alternative to bone marrow transplantation in the treatment of severe aplastic anaemia.

Adolescent↗
PubMed1983

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VI. Effects of stroma-free hemoglobin and red blood cell stroma on mortality and neutrophil function.

Hemoglobin is known to increase the lethality of experimental E. coli peritonitis, but its mechanism of action has not been defined. Some evidence from this laboratory previously suggested that hemoglobin could interfere with local leukocyte function in the peritoneal cavity. In the present study we compared the effect of impure bovine hemoglobin, highly purified stroma-free hemoglobin, and red blood cell stroma on the mortality rate of rats with Escherichia coli peritonitis, as well as on human neutrophil function in vitro. Both hemoglobin preparations markedly increased the mortality rate at low bacterial concentrations. Red blood cell stromal elements increased the rate to a minimal degree and only at high bacterial concentrations. The character of the E. coli-induced peritoneal leukocytosis was not significantly affected by concomitant administration of either stroma-free hemoglobin or red blood cell stroma. Although crystalline bovine hemoglobin inhibited in vitro leukocyte chemotaxis, centrifugation of this preparation to remove debris abrogated this effect. Stroma-free hemoglobin had no effect on in vitro leukocyte chemotaxis. Red blood cell stromal elements in high concentration diminished phagocytosis and bacterial killing by human neutrophils, but stroma-free hemoglobin had no effect on these neutrophil functions. The results confirm that hemoglobin is a potent adjuvant in experimental E. coli peritonitis, but contrary to our previous conclusion does not owe this effect to direct interference either with neutrophil influx into the peritoneal cavity during bacterial peritonitis or with human leukocyte function in vitro. Such prior conclusions appear to have been based on insoluble material including stromal elements in the hemoglobin preparations used. Red cell stromal elements derived from as little as 1 ml of packed red cells can significantly interfere with the phagocytosis and killing of E. coli.

Animals↗
PubMed1983

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VII. Hemoglobin does not inhibit clearance of Escherichia coli from the peritoneal cavity.

Hemoglobin has been shown to be a potent adjuvant in experimental Escherichia coli peritonitis, although a satisfactory mechanistic rationale is still obscure. Hemoglobin has been thought to impair intraperitoneal neutrophil function, delay clearance of bacteria from the peritoneal cavity by the normal absorptive mechanisms, or directly enhance bacterial growth. Using highly purified stroma-free hemoglobin (SFHgb), we have largely discounted any direct effect of hemoglobin on peritoneal white blood cell function. In the present study, we confirmed that uncontrolled proliferation of bacteria takes place in the presence of hemoglobin in the peritoneal cavity. Nonviable 5-iododeoxyuridine 125I-labelled bacteria were then used to directly study peritoneal clearance kinetics, eliminating the problem of bacterial growth. SFHgb had no influence on the removal of intraperitoneal bacteria. The rate of bloodstream appearance of radiolabel was similar with or without intraperitoneal SFHgb. Thus, SFHgb does not prevent clearance of bacteria from the peritoneal cavity by interfering with normal host clearance mechanisms. SFHgb may act as a bacterial growth adjuvant, either by serving as a bacterial nutrient or by suitably modifying the environment so that extensive bacterial proliferation can occur. The latter hypothesis appears to be an area in which investigation concerning the adjuvant effect of hemoglobin may prove most fruitful.

Animals↗
PubMed1982

Prophylaxis of CMV infection in bone marrow transplant recipients by hyperimmune CMV gamma-globulin.

Prophylactic administration of an intravenous hyperimmune CMV IgG in bone marrow transplant recipients resulted in the complete protection against development of CMV infections and interstitial pneumonia. Incidence of severe graft versus host disease was markedly reduced and there was no mortality in the CMV IgG group. Mortality in those receiving standard supportive therapy was 27%. The source of hyperimmune plasma, method of fractionation and properties of the IgG are described. The effectiveness of this hyperimmune CMV IgG is related to the high content of antiviral antibodies, the dosage, the fact that it is intact, 99% monomeric, and essentially devoid of the IgG3 subclass. The timing of administration together with its effectiveness suggests this preparation might be effective in the treatment of established disseminated CMV infections.

Adolescent↗
PubMed1981

Clinical and secretory differences in pancreatic cancer and chronic pancreatitis.

The differential diagnosis between chronic pancreatitis and pancreatic cancer can be very difficult. In 60 patients with either of these conditions, who had satisfactory ERCP study, clinical features were correctly matched with the final diagnosis by discriminant analysis in 44 (73%). The sensitivity of ERCP radiographic findings in pancreatic cancer was 80% and sensitivity of cytology was 54%. To see if exocrine function was specific for cancer, fresh pancreatic secretions were aspirated in 27 patients at the time of ERCP. By isoelectric focusing, a pattern of extreme zymogen depletion was observed in chronic alcoholic pancreatitis (Group 1), pancreatic cancer (Group 2), and chronic nonalcoholic pancreatitis (Group 3). The three groups were not distinguishable. By contrast, significant changes in albumin, IgG and IgA concentrations were seen in Group 2. The albumin level was over ten-fold greater than in Groups 1 and 3 (p less than 0.02 and less than 0.05). The IgG was seven-fold and two-fold greater (p less than 0.01 and greater than 0.2) and the IgA was 15-fold and six-fold greater (p less than 0.002 and less than 0.05) than in Groups 1 and 3, respectively. The two groups of pancreatitis had similar concentrations of albumin and IgA. The ratio of albumin to IgG was also different in Group 2 from the other groups, suggesting different mechanisms for the appearance of proteins in pancreatic secretions. Nonzymogen protein levels can distinguish chronic pancreatitis from pancreatic cancer, and further study of them may identify useful tumor-specific markers.

Albumins↗