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Biomedical subjects

W G Ho

Publications and source records attributed to W G Ho.

At least 37 records · Page 2Linked to original sources

Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients.

The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.

Adolescent↗

Recombinant interferon alpha-2a for treatment of herpes zoster in immunosuppressed patients with cancer.

PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.

Adult↗

Plasma exchange for recurrent nephrotic syndrome following renal transplantation.

Patients with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FGS) who develop end-stage renal disease are at risk for recurrence of the disease following renal transplantation. Recurrence of the nephrotic syndrome in renal allografts of two children with primary FGS was successfully controlled by plasma exchange. This report suggests that plasma exchange instituted early in the course of recurrent nephrotic syndrome may be beneficial in some patients with steroid-resistant nephrotic syndrome and FGS.

Adolescent↗

Prophylaxis of infection in bone marrow transplants.

Bone marrow transplants experience severe immuno-deficiency as a consequence of pretransplant radiation and chemotherapy, transient granulocytopenia before marrow engraftment, and post-transplant prevention and treatment of graft-versus-host disease with immuno-suppressive agents. During periods of granulocytopenia, chemoprophylaxis with the oral fluorinated quinolones can prevent colonization and infection with gram-negative bacilli, is better tolerated than oral non-absorbable antibiotics or trimethoprim-sulfamethoxazole and is more cost-effective than laminar-air-flow isolation or prophylactic granulocyte transfusions. Antifungal prophylaxis with oral nystatin, ketoconazole or amphotericin B, however, has not been consistently effective; empiric intravenous amphotericin B therapy is still the most reliable way to prevent fatal fungal infections. Following marrow engraftment, cytomegalovirus infection and interstitial pneumonia can be prevented in cytomegalovirus-seronegative patients by the use of cytomegalovirus-seronegative blood products and cytomegalovirus immune globulin. In cytomegalovirus-seropositive patients, prophylactic DHPG (ganciclovir) is currently being evaluated in a controlled clinical trial. Herpes simplex and varicella-zoster infections can be treated effectively with intravenous acyclovir, but routine acyclovir prophylaxis is not cost-effective. Trimethoprim-sulfamethoxazole is used for prophylaxis of Pneumocystis carinii pneumonia and may be continued in patients with chronic graft-versus-host disease for prevention of late post-transplant bacterial infections.

Agranulocytosis↗

Norfloxacin for prevention of bacterial infections in granulocytopenic patients.

The efficacy and safety of norfloxacin were compared with those of placebo, vancomycin-polymyxin, and trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis of bacterial infections in granulocytopenic patients. The study results showed that norfloxacin treatment, which was well tolerated and not associated with any serious systemic adverse effects, prevented acquisition of gram-negative bacillary organisms. Fewer norfloxacin-treated patients (38 of 108 patients, or 35 percent) experienced microbiologically documented infections compared with patients receiving placebo (27 of 40 patients, or 68 percent), vancomycin-polymyxin (16 of 30 patients, or 53 percent), or TMP/SMX (14 of 28 patients, or 50 percent). Gram-negative bacteremia developed in five of 108 norfloxacin-treated patients (5 percent), compared with 17 of 40 placebo-treated patients (43 percent), five of 30 treated with vancomycin-polymyxin (17 percent), and one of 28 patients treated with TMP/SMX (4 percent). The incidence of gram-positive bacteremia was similar in all study groups and was not affected by norfloxacin or any other oral prophylactic antibiotics. These results suggest that norfloxacin is both safe and effective for the prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive bacterial infections, however, is needed.

Adolescent↗

Bone marrow transplantation in patients with leukaemia previously transfused with blood products from family members.

Transfusions are withheld, whenever possible, from patients with aplastic anaemia who are potential bone marrow transplant recipients because of the increased risk of graft failure associated with transfusions prior to transplantation. Family members are specifically excluded as blood product donors to reduce the likelihood of sensitizing the recipient to antigens shared by the blood and bone marrow donor. This policy of not using family members, particularly the HLA-matched bone marrow donor, to provide blood products prior to transplantation has been extended to leukaemia as well. To evaluate this policy we reviewed the outcome of bone marrow transplantation in 18 patients with leukaemia transfused prior to transplantation with platelets and/or leucocytes from related family members. In 15 cases in which the outcome could be evaluated, engraftment was rapid and graft failure did not occur. Transfusion of blood products from related family members to patients with leukaemia prior to transplantation does not appear, therefore, to increase the risk of graft rejection.

Blood Donors↗

Multiple molecular abnormalities in Ph1 chromosome positive acute lymphoblastic leukaemia.

The Ph1 chromosome is present in 95% of patients with chronic myelogenous leukaemia (CML). The Ph1 chromosome also occurs in 5-25% of children and adults with acute lymphoblastic leukaemia (ALL). This observation raises questions as to whether these diseases are similar or identical. In patients with CML the c-abl and bcr genes are translocated and abnormally expressed. We studied molecular events related to bcr and c-abl in five patients with ALL to determine its relationship to CML. Four had the Ph1 chromosome; the fifth a probable Ph1 chromosome. c-abl and bcr abnormalities identical to CML were detected in four suggesting a common molecular basis. One patient with the Ph1 chromosome and c-abl translocation lacked these molecular changes but had abnormal c-abl gene transcription apparently unrelated to bcr. These data suggest that Ph1 chromosome positive ALL is heterogeneous; in some patients the molecular abnormality is identical to CML; in others c-abl is likewise involved but via a different mechanism.

Adolescent↗

Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation.

The effects of high doses of polyvalent intravenous immune globulin given for prophylaxis of cytomegalovirus infection and interstitial pneumonia in recipients of allogeneic marrow transplants were evaluated in a randomized controlled trial. Both symptomatic cytomegalovirus infection (21% compared with 46%, p = 0.03) and interstitial pneumonia (18% compared with 46%, p = 0.02) occurred less frequently in the recipients of intravenous immune globulin than in control patients. Prophylactic intravenous immune globulin was also associated with a lower incidence of graft-versus-host disease (34% in recipients compared with 65% in controls, p = 0.01), but its reduction in rates of interstitial pneumonia was independent of graft-versus-host disease and occurred in both patients with and without graft-versus-host disease. The high doses of immune globulin were well tolerated. Prophylactic intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia and possibly graft-versus-host disease in patients having allogeneic marrow transplantation.

Adolescent↗

Norfloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients.

Selective antimicrobial decontamination with norfloxacin was compared with vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients. In the group of patients receiving norfloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.88 versus 1.86, p = 0.002), fewer patients with documented infection (16 of 36 versus 20 of 30, p = 0.12), and fewer cases of gram-negative septicemia (0 of 36 versus five of 30, p = 0.02). Norfloxacin was better tolerated (30 of 36 versus 16 of 30 patients highly compliant, p = 0.02), and associated with fewer gastrointestinal side effects (eight of 36 versus 14 of 36 patients, p = 0.07). These results suggest that norfloxacin is a more tolerable and efficacious oral antimicrobial agent than vancomycin/polymyxin for the prevention of serious gram-negative bacillary infections in granulocytopenic patients.

Adolescent↗

Ureidopenicillins, aztreonam, and thienamycin: efficacy as single-drug therapy of severe infections and potential as components of combined therapy.

The ureidopenicillins (piperacillin, mezlocillin, and azlocillin), aztreonam, and thienamycin are new broad-spectrum beta-lactams with more potent antibacterial activity than the older cephalosporins and penicillins. However, therapy of severe infections with the ureidopenicillins alone is limited by the potential for emergence of resistant organisms, while monotherapy with aztreonam does not provide adequate coverage for Gram-positive aerobic organisms and anaerobes. In combination therapy with the aminoglycosides, the ureidopenicillins may be preferred to carbenicillin or ticarcillin in the treatment of Pseudomonas aeruginosa infections and in institutions with a high prevalence of carbenicillin or ticarcillin-resistant organisms. Double beta-lactam therapy with piperacillin plus either latamoxef (moxalactam) or ceftazidime may be advantageous in patients for whom aminoglycoside toxicity is a concern. Thienamycin is the most promising of the new beta-lactams for single-agent therapy of severe infections but may also be associated with the emergence of resistant P. aeruginosa during monotherapy. In febrile granulocytopenic patients or other severely ill patients at risk of severe P. aeruginosa infections, thienamycin or another antipseudomonal beta-lactam should be combined with an aminoglycoside.

Aminoglycosides↗

Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial.

The effects of ex-vivo depletion of T lymphocytes from donor bone marrow using a monoclonal anti-T-cell antibody (CT-2) and complement on the outcome of allogeneic bone marrow transplantation was evaluated in a prospective, randomized, double-blind study of 40 patients with leukemia. Patients receiving T-cell-depleted bone marrow had a lower incidence of acute graft-versus-host disease than control patients (3 of 20 compared with 13 of 20; p = 0.004), and mortality due to acute graft-versus-host disease was reduced. Five patients in the T-cell-depletion group developed graft failure; all control patients had sustained engraftment (p less than 0.05). Clinically apparent relapse of leukemia occurred in 7 patients from the T-cell-depletion group and in 2 controls (p, not significant). Cytogenetic evidence of residual leukemia was also detected in the 5 patients with graft failure without overt relapse. Infections and overall survival were similar in the two groups. The effects of T-cell depletion on engraftment and recurrence of leukemia require further evaluation.

Actuarial Analysis↗

Infection and transfusion therapy in acute leukaemia.

Granulocytopenia is the single most important risk factor for infection in patients with acute leukaemia. There are limitations to the effective prophylaxis of infection in granulocytopenic patients, but practical measures include the management of the patient in a private hospital room, the requirement of all medical personnel and visitors to wash their hands carefully and to wear masks, restricting the patient to a low-bacteria diet devoid of fresh fruit, vegetables and salads, and the administration of oral antimicrobial agents for gastrointestinal decontamination. When fever develops, empirical therapy with a combination of an aminoglycoside plus an antipseudomonal beta-lactam should be started promptly. A double beta-lactam combination of cefoperazone or ceftazidime plus piperacillin can be substituted if nephrotoxicity is a concern. The addition of empirical intravenous amphotericin may be useful in patients who remain febrile and granulocytopenic on broad-spectrum antibiotics, especially if surveillance cultures indicate fungal colonization. Amphotericin is also the most reliable agent for the treatment of established fungal infections. Acyclovir is not recommended for prophylaxis in acute leukaemia patients but should be reserved for the treatment of well-documented and clinically significant herpes simplex viral infections. During periods of remission, most patients with AML remain free of infection except when they become granulocytopenic again during intensification or consolidation chemotherapy. On the other hand, children with ALL in remission may experience frequent infections unrelated to granulocytopenia as a consequence of their maintenance chemotherapy. Pneumocystis carinii, varicella zoster, and other viruses are common pathogens. Trimethoprim-sulphamethoxazole is effective prophylaxis against Pneumocystis carinii pneumonia in patients with ALL, while intravenous acyclovir is the drug of choice for treatment of varicella zoster infection. Transfusion therapy in the acute leukaemia patient is guided by the patient's peripheral blood counts and degree of sensitization to blood products. Generally, packed red blood cells are given in order to maintain the haematocrit at greater than 30%, while random-donor platelets are administered to keep the platelet count at greater than 20 X 10(9)/l. If refractoriness to platelet transfusions develops, HLA-matched platelets from family members or selected unrelated donors can be used. Similarly, washed or filtered red blood cells may be given to patients with previous and recurrent non-haemolytic febrile reactions to red blood cell transfusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Molecular epidemiology of cytomegalovirus infections associated with bone marrow transplantation.

Restriction endonuclease analysis of purified viral DNA was used to study the molecular epidemiologic characteristics of cytomegalovirus infection in 18 patients having bone marrow transplantation. Four patients who had had asymptomatic excretion of cytomegalovirus in urine before transplantation subsequently developed a cytomegalovirus infection after transplantation (pneumonia in 2 patients, fever and viremia in 1 patient, and asymptomatic viruria in 1 patient). In each patient, the infection that developed after transplantation was caused by a cytomegalovirus strain genetically identical to the isolate detected in urine before transplantation. Cytomegalovirus isolates from different sites (buffy coat, lung, and urine) of the same patient were also identical, but cytomegalovirus isolates from different patients were never identical. Our results suggest that some cytomegalovirus infections after bone marrow transplantation may be caused by strains present before transplantation. The great structural and genetic variability of cytomegalovirus isolates must be considered in the development of effective diagnostic and immunoprophylactic measures for infection after marrow transplantation.

Adolescent↗

Treatment of acute myelogenous leukemia. A prospective controlled trial of bone marrow transplantation versus consolidation chemotherapy.

In a prospective controlled trial, the relative effectiveness of allogeneic bone marrow transplantation and postremission chemotherapy was assessed for adult patients with acute myelogenous leukemia in first complete remission. Twenty-three patients, 15 to 45 years of age, who had an HLA-identical sibling donor were designated to receive bone marrow transplantation. Forty-four patients who either lacked an HLA-identical sibling or were over 45 years of age were designated to receive intensive consolidation chemotherapy. The actuarial rate of leukemia relapse was significantly lower in the transplantation group than in the chemotherapy group (40 +/- 25% [95% confidence interval] compared with 71 +/- 14%, p = 0.01). Actuarial survival at greater than 4 years was not significantly different (40 +/- 21% compared with 27 +/- 14%, p greater than 0.4). These data show that bone marrow transplantation is more effective than consolidation chemotherapy in preventing leukemia relapse, but overall survival was not improved in this study.

Adolescent↗