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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 181 records · Page 10Linked to original sources
PubMed1988

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↗
PubMed1988

Treating multiple sclerosis with monoclonal antibodies: the cons.

The clinical use of monoclonal antibodies (MAbs) in multiple sclerosis (MS) is an exciting clinical prospect whose current use is subject to several limitations. Clinical studies to date have shown that infusion of murine MAbs, the preparations presently available, is associated with the production of antimurine antibody, which makes the long-term use of this therapy infeasible in most patients. This is a considerable drawback in a chronic progressive disease such as MS, where retreatment options are an important consideration in choice of therapy. In addition, most murine MAbs are not lytic for targeted cells. The target antigens often undergo modulation and the cells reappear in the circulation with full function in spite of ongoing therapy. The use of MAbs in MS needs further clarification through randomized, controlled clinical trials.

Animals↗
PubMed1987

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↗
PubMed1987

Sustained recovery of hematopoiesis and immunity following transplantation of fetal liver cells in dogs.

We studied the ability of fetal liver cells to reconstitute hematopoiesis and immunity in lethally irradiated dogs. Engraftment and sustained lymphoid and hematopoietic recovery was achieved when the recipients received a preparative regime of high-dose total body irradiation (TBI) alone followed by transplantation of DLA-identical fetal liver. The combination of high-dose TBI and cyclosporine allowed engraftment in DLA-mismatched fetal liver transplants. Typical features of graft-versus-host disease (GvHD) did not occur although autoimmune-like syndromes (myasthenia gravis, immune thrombocytopenia) were observed in some recipients. Hematopoietic recovery was rapid and complete. Recovery of T- and B-lymphocyte function was comparatively delayed, but sufficient to prevent opportunistic infections after the initial 3 months post transplant. These data indicate that cells from a single fetal liver can reconstitute hematopoiesis and immunity in DLA-mismatched recipients and suggest that human fetal liver cell transplantation may be an effective source of stem cells for patients who lack an HLA-identical donor for bone marrow transplantation.

Animals↗
PubMed1987

Treatment of cytomegalovirus retinopathy with ganciclovir.

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

Designed transfer of specific immune responses with bone marrow transplantation.

Bone marrow transplant donors were immunized with tetanus/diphtheria toxoids 6-7 d before bone marrow donation to investigate the role of B cell subpopulations in reconstitution of humoral immunity. Lymphoblastoid B cells spontaneously producing IgG antitetanus and/or antidiphtheria toxoid were detected in the donor marrows at the time of transplantation. Recipients rapidly demonstrated 3-90-fold increases in serum IgG antitetanus and antidiphtheria toxoid levels. Antidiphtheria fragment A antibody in three donor/recipient pairs demonstrated spectrotypic identity indicating transfer of the donors' response. Reimmunization of three recipients 64-154 d after transplant revealed an IgG antibody response associated with reappearance of spontaneous antibody-producing B cells and an antidiphtheria fragment A response characteristics of the donor's immune response. These observations extend the understanding of the role of B cell subpopulations and provide a basis for specific modulation of immunity in the setting of bone marrow transplantation.

Adult↗
PubMed1986

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↗
PubMed1986

Bone marrow transplantation in acute leukaemia.

Bone marrow transplantation is useful in AML. Results of chemotherapy and transplantation are compared in Table 4. Transplantation is the preferred treatment in individuals who fail chemotherapy. Transplantation is also likely to be superior or comparable to chemotherapy in individuals less than 30 years of age in first remission. Transplantation in older individuals in first remission is controversial, but it is unlikely that these results are inferior to results with chemotherapy. Transplants from donors other than HLA-identical siblings are less well investigated but may be a reasonable alternative in young individuals in first relapse or second remission, particularly if recipient and donor share most HLA antigens. Autotransplants are difficult to evaluate critically and should be considered investigational in individuals in second or later remission for whom a suitable donor is unavailable. Autotransplants in first remission should be restricted to controlled clinical trials, since their efficacy is otherwise inevaluable. It is uncertain whether in vitro treatment of the bone marrow is necessary in the context of autotransplantation; again, controlled trials are required. Bone marrow transplantation from an HLA-identical sibling is a useful therapy in individuals with ALL who relapse despite chemotherapy. Individuals undergoing transplantation in second or later remission or in relapse have a survival rate superior to those treated with chemotherapy; these data are summarized in Table 5. One important unresolved issue in ALL is whether children with high-risk ALL and adults should receive transplants in first remission. This answer will, to a considerable extent, depend on results achieved with chemotherapy alone. If intensive chemotherapy produces 50-70% disease-free survival in these individuals, it is unlikely that transplantation will be superior. If, however, alternative chemotherapy results are inferior, transplantation may be useful. Clearly, controlled clinical trials are needed. Results of transplants from donors other than HLA-identical siblings are less certain but this approach may be considered in selected young individuals who fail chemotherapy. Autotransplants should also be considered in this setting but not in individuals in first remission. It is likewise uncertain if in vitro treatment of the bone marrow is useful; this must be addressed in controlled trials. The data reviewed indicate an important role for bone marrow transplantation in the therapy of the acute leukaemias. We have attempted to precisely define its use in various disease states.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow Transplantation↗