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Biomedical subjects

W G Ho

Publications and source records attributed to W G Ho.

At least 55 records · Page 3Linked to original sources

[Use of a polyvalent intravenous immunoglobulin or specific cytomegalovirus hyperimmunoglobulin for modification of cytomegalovirus infections and prevention of interstitial pneumonias following bone marrow transplantation].

The effects of prophylactic, polyvalent intravenous immune globulin on cytomegalovirus infection and interstitial pneumonia in allogenic marrow transplants were evaluated in an ongoing, randomized controlled trial. Thirty-eight patients were given weekly doses (20 cc/kg) of polyvalent intravenous immune globulin before and after transplantation, and 37 patients were controls. Both symptomatic cytomegalovirus infection (17 of 37 or 46% vs. 8 of 38 or 21%, p = 0.04) and interstitial pneumonia (17 of 37 or 46% vs. 7 of 38 or 18%, p = 0.02) occurred less frequently in the recipients of polyvalent intravenous immune globulin. In separate kinetic studies, a 5 cc/kg dose of a cytomegalovirus-specific hyperimmune globulin produced cytomegalovirus antibody titers in patients equivalent to those achieved after the 20 cc/kg dose of polyvalent intravenous immune globulin. All immune globulin preparations were well-tolerated. These preliminary results suggest that intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in marrow transplants. Additional trials are now needed to define the minimal effective dose of intravenous immune globulin and to compare the effectiveness of different intravenous immune globulin formulations.

Anemia, Aplastic↗

Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial.

We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.

Adolescent↗

Intravenous immunoglobulin for modification of cytomegalovirus infections associated with bone marrow transplantation. Preliminary results of a controlled trial.

The effects of immune globulin intravenous, 5 percent in 10 percent maltose, on cytomegalovirus infection and interstitial pneumonia in bone marrow transplants were evaluated in a randomized controlled trial. Eighteen patients were given weekly doses (20 cc/kg) of intravenous immunoglobulin before and after transplantation, and 18 patients were controls. The incidence of cytomegalovirus infection was similar in the control and intravenous immunoglobulin-treated groups, but symptomatic cytomegalovirus infection (eight of 18 versus three of 18, p = 0.14) and interstitial pneumonia (10 of 18 versus four of 18, p = 0.08) occurred less frequently in the group receiving intravenous immunoglobulin. Cytomegalovirus pneumonia developed in eight control patients and in three patients receiving intravenous immunoglobulin (p = 0.14), whereas two control patients and one patient receiving intravenous immunoglobulin experienced idiopathic interstitial pneumonia. These preliminary results suggest that intravenous immunoglobulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in bone marrow transplant recipients.

Adolescent↗

Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients.

In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy. Most patients were also given prophylactic vitamin K. The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin). For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P. aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P. aeruginosa isolates. On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02). Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28). There was no antibiotic-related hemorrhage. These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar. Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P. aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy.

Adolescent↗

Transplantation of ABH incompatible bone marrow: gravity sedimentation of donor marrow.

A simple technique to separate erythrocytes from bone marrow by sedimentation under gravity after addition of hydroxyethyl starch is described. This method of removing red blood cells from the donor marrow was evaluated in 23 consecutive allogeneic bone marrow transplants between ABH-incompatible individuals. Infusion of the separated marrow was well tolerated, i.e. graft-rejection did not occur, and sustained engraftment was documented in all evaluable cases. This technique obviates the need for cumbersome and potentially hazardous large volume plasma exchange that is commonly utilized to deplete recipient isohaemagglutinins prior to transplantation.

ABO Blood-Group System↗

Safety and tolerance of recombinant leukocyte A interferon in bone marrow transplant recipients.

Five bone marrow transplant recipients with cytomegalovirus infections were treated with pure recombinant leukocyte A interferon produced by recombinant DNA technology from Escherichia coli. All five patients had documented interstitial pneumonia. The daily intramuscular dose of interferon ranged from 18 X 10(6) to 50 X 10(6) U; the mean duration of therapy was 11.0 days (range, 5 to 18 days). Two patients recovered, one improved, and two died. Clinical side effects (usually fever and chills) occurred in three patients. A 60% or greater reduction in the pretherapy peripheral granulocyte counts occurred in four patients, and four patients had a 37 to 80% reduction in their pretherapy platelet counts. Hematological toxicity was reversible, and there was no loss of marrow graft function. The toxicity of pure recombinant leukocyte A interferon in marrow transplants is similar to that of partially pure leukocyte interferon derived from human cells. Further controlled studies to establish the efficacy of recombinant leukocyte A interferon in marrow transplants are warranted but may be limited by hematological toxicity.

Adult↗

Pneumococcal vaccination of recipients of bone marrow transplants.

A 14-valent pneumococcal vaccine was administered to 39 recipients of allogeneic bone marrow transplants, and their type-specific antibody responses were compared with normal control subjects. Preimmunization antibody levels in patients were twofold to 12-fold lower than those levels in control subjects for all serotypes. Mean postimmunization antibody levels for each serotype were also considerably lower in patients (range, 56 to 859 ng of antibody nitrogen per milliliter) than in control subjects (range, 727 to 5,626 ng/mL). Poor antibody responses were primarily associated with early vaccination after transplantation, corticosteroid therapy for graft-v-host disease and other illnesses, and the male sex. Antibody responses of patients not given corticosteroids and vaccinated more than seven months after transplantation improved with time after transplantation. Postvaccination infection occurred in five patients who were vaccinated early after transplantation. Pneumococcal vaccination has limited potential for providing protection in marrow transplant recipients except in the cases of those patients who are not receiving corticosteroids and are vaccinated more than seven months after transplantation.

Adolescent↗

Coagulase-negative staphylococcal bacteremia in patients receiving immunosuppressive therapy.

From January 1977 to June 1980, coagulase-negative staphylococci caused bacteremia in 22 (17%) of 130 patients receiving immunosuppressive therapy and were the most common cause of all bacteremias. Sixteen (73%) of the 22 patients had granulocytopenia, and eight were isolated in a laminar air-flow room. A Broviac or Hickman central intravenous (IV) catheter was present in 20 (91%) of 22 patients, and soft-tissue inflammation at the catheter exit site was a significant risk factor for bacteremia. Except for debilitating fevers and local mucocutaneous infections, there were no distinguishing clinical features in patients with bacteremia. Most infections responded to cefazolin sodium or vancomycin hydrochloride therapy; catheter removal was necessary in only seven patients. These data show that coagulase-negative staphylococci can be important pathogens in patients receiving immunosuppressive therapy, even when the patients are isolated in a laminar air-flow room, if normal mucocutaneous, host-defence barriers are interrupted by IV catheter-insertion or chemotherapy.

Adolescent↗

Use of intravenous immune globulin in patients receiving bone marrow transplants.

Patients undergoing bone marrow transplantation for acute leukemia or aplastic are a great risk for the development of interstitial pneumonia associated with the cytomegalovirus (CMV). Passive immunization with a CMV immune plasma has been found to be effective for the prevention of interstitial pneumonia after marrow transplantation. Because of the limited availability of high-titered CMV plasma, we studied the kinetics of CMV antibody in bone marrow transplant patients receiving immune globulin intravenous, 5%, in 10% maltose (IGIV). Several lots of IGIV had CMV radioimmunoassay (RIA) antibody titers (1:30,000) comparable to the CMV antibody titers in the CMV immune plasma. A single infusion of 20 cc/kg of IGIV produced a mean peak CMV RIA antibody titer of 1:9,500. This titer fell to 1:1,000 after seven days. These antibody titers were approximately two-to three-fold lower than the CMV RIA antibody titers achieved after a 10 cc/kg dose of the CMV immune plasma. Administration of IGIV at doses lower than 20 cc/kg produced correspondingly lesser increases in the CMV antibody titers of recipients. At all doses, IGIV was well tolerated and caused no significant biochemical abnormalities. Some patients experienced mild elevation of their serum glucose levels and asymptomatic glycosuria. We are presently evaluating the efficacy of IGIV (20 cc/kg given once every week) for the modification of CMV infection and prevention of interstitial pneumonia after bone marrow transplantation in a randomized, controlled study. The effects of IGIV on the incidence and outcome of bacterial, fungal, and other viral infections are also being analyzed.

Antibodies, Viral↗

Alveolar macrophage dysfunction in human bone marrow transplant recipients.

We studied the functional characteristics of alveolar macrophages obtained by segmental pulmonary lavage from allogeneic marrow transplant recipients without evidence of ongoing pulmonary infection. The macrophages were mostly of donor marrow origin as judged by Y body fluorescence and were morphologically normal, except for the intracellular accumulation of various amounts of heterogeneous foreign materials. Macrophage function of patients studied within four months after transplantation was impaired, as measured by chemotaxis, phagocytosis and killing of Candida pseudotropicalis, and killing of bacteria. In two patients studied six and 12 months after transplantation, macrophage functions returned toward normal except for a persistent defect in killing of C. pseudotropicalis. Cytomegalovirus was cultured from the lavaged cells of two patients, but the macrophage dysfunction was independent of the cytomegalovirus isolation. These results show that alveolar macrophage dysfunction occurs in marrow transplant recipients and may be associated with their increased risk for pulmonary infections.

Acute Disease↗

Ineffectiveness of aspirin and dipyridamole in the treatment of thrombotic thrombocytopenic purpura.

Platelet-inhibiting drugs have been used widely in the treatment of thrombotic thrombocytopenia purpura. Nineteen consecutive patients received various treatments including platelet inhibitors, glucocorticoid drugs, whole blood or plasma exchange transfusions, and splenectomy. During treatment with aspirin and dipyridamole in 14 patients, five died, and only one had neither new neurologic signs nor worsening thrombocytopenia. Prostacyclin in one patient was not beneficial. Serious bleeding complications, including massive upper gastrointestinal hemorrhage, epistaxes, or subarachnoid hemorrhage confirmed at autopsy, occurred in five of the 19 patients and only during treatment with aspirin and dipyridamole. We conclude that there is no evidence for the effectiveness of aspirin and dipyridamole in the treatment of thrombotic thrombocytopenic purpura and that these drugs may increase the risk of serious bleeding complications.

Adolescent↗

Cytomegalovirus immune plasma in bone marrow transplant recipients.

The effects of passive immunization on cytomegalovirus infection and interstitial pneumonia in marrow transplants were evaluated in a randomized, controlled trial. Twenty-four patients received cytomegalovirus immune plasma before and after transplantation, and 24 patients were controls. Although the incidence of cytomegalovirus infection was similar in the control and plasma groups, symptomatic infection (12 of 24 versus five of 24, p = 0.07) and interstitial pneumonia (11 of 24 versus five of 24, p = 0.12) occurred less frequently in the group receiving plasma. Cytomegalovirus infection occurred in 11 of 13 recipients of leukocyte transfusions and in 16 of 35 patients not given leukocyte transfusions (p = 0.02). Among patients not given leukocyte transfusions, the incidence of cytomegalovirus infection was similar in the control and plasma groups, but symptomatic infection (eight of 18 versus one of 17, p = 0.03) and interstitial pneumonia (nine of 18 versus one of 17, p = 0.01) were significantly less in the group receiving plasma. These results suggest that passive immunization modifies cytomegalovirus infection in humans and prevents interstitial pneumonia in marrow transplants especially when leukocyte transfusions are not used.

Adolescent↗

Therapeutic granulocyte transfusions for documented infections. A controlled trial in ninety-five infectious granulocytopenic episodes.

Patients with granulocytopenia (granulocyte count less than 0.5 x 10(9)/L) and a documented infection were randomized to receive or not to receive daily granulocyte transfusions in addition to antimicrobial therapy. Thirty-four of 47 control patients responded to therapy compared to 30 of 48 transfused patients (type 2 error, pneumonia, or a soft tissue infection, respective response rates for the control and transfused patients were 11 of 11 and 11 of 16 (Yates' corrected chi-squared test, p = 0.12). Response rates for patients with gram-negative septicemia were lower but were influenced by recovery of bone marrow function. Eleven of 12 control patients and seven of seven transfused patients with recovery of marrow function survived the gram-negative septicemia. In contrast, 12 of 24 control patients and 12 of 25 transfused patients survived gram-negative septicemia and persistent granulocytopenia (type 2 error p = 0.13). Two thirds of all fatal infections were associated with an underlying disease refractory to medical therapy. Therapeutic granulocyte transfusions had no substantial benefit over optimal antimicrobial therapy alone in managing infected patients with granulocytopenia.

Abscess↗

Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.

In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.

Adolescent↗

High-dose combined-modality therapy and autologous bone marrow transplantation in resistant cancer.

Fourteen patients with resistant cancers received high-dose chemotherapy and total body irradiation followed by rescue with autologous cryopreserved bone marrow cells. In seven patients, disease has remained in remission for periods up to two years. These data indicate that effectiveness of high-dose combined-modality therapy and bone marrow autotransplantation in patients with resistant cancer. The high incidence of non-marrow toxicity may be reduced by the use of this modality before patients have received extensive therapy.

Adolescent↗

Prophylactic granulocyte transfusions during chemotherapy of acute nonlymphocytic leukemia.

Forty-six noninfected patients undergoing induction chemotherapy for acute nonlymphocytic leukemia were randomized to receive (25 patients) or not to receive (21 control patients) prophylactic granulocyte transfusions when their granulocyte count fell below 0.5 X 10(9)/L. Septicemia was less frequent in the patients who received transfusions (two in 25 patients) than in the control patients (five in 21 patients), but this difference was not statistically significant (p = 0.28). Moreover, pneumonia was more frequent among the transfused patients (12 in 25 patients versus two in 21 patients, p = 0.01). There were no significant differences between the two groups in the frequency of other documented infections, the achievement or duration of remission, or survival. Recipients of prophylactic granulocyte transfusions had a higher prevalence of cytomegalovirus infections (13 in 21 patients versus five in 19 patients, p = 0.03). These results suggest that prophylactic granulocyte transfusions have no statistically significant effect on the frequency of septicemia or other infections, do not enhance remission rates or survival, and are associated with an increased risk for pulmonary complications and cytomegalovirus infections.

Adolescent↗

Prophylactic granulocyte transfusions during human bone marrow transplantation.

Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients.

Adolescent↗