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D Emanuel

Publications and source records attributed to D Emanuel.

35 records · Page 2Linked to original sources
PubMed1991

Successful management of CMV pneumonia in a mechanically ventilated patient.

We report a case of severe respiratory failure due to cytomegalovirus pneumonitis in a patient who underwent an allogeneic bone marrow transplant, who was successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. We also reviewed the rationale for the use of combination therapy with an antiviral agent and immunotherapy. Because of the bone marrow toxicity of ganciclovir, an aggressive diagnostic approach, including bronchoalveolar lavage and open lung biopsy, may be necessary to establish a definitive diagnosis prior to institution of therapy.

Adult↗
PubMed1990

Treatment of cytomegalovirus disease.

Cytomegalovirus (CMV) infection, particularly CMV pneumonitis, continues to be an important infectious complication following allogeneic bone marrow transplantation. Most bone marrow transplant (BMT) centers have reported an overall incidence of CMV pneumonitis of 15% to 20%. Until recently, the mortality rate from CMV pneumonitis has been extremely high (greater than 80%). Historically, both single-agent therapy and combination treatments have failed to increase survival of BMT recipients with CMV pneumonia. The introduction of new antiviral agents with potent activity against CMV in vitro, such as ganciclovir and trisodium phosphonoformate, seemed to offer promise for improving survival. However, as single agents, a significant impact on mortality has not been achieved with either. The addition of high-dose intravenous immunoglobulin (IVIG) to ganciclovir appears to have a significant impact on mortality due to CMV pneumonia following bone marrow transplantation. The mechanism by which IVIG exerts its clinical effect remains to be determined, and a better understanding of the underlying process may improve this approach in the future. Bone marrow toxicity associated with ganciclovir remains a particular problem in the BMT population. Strategies to circumvent this problem, such as the use of hematopoietic stem cell growth factors or the use of an agent that is less bone marrow suppressive, such as phosphonoformate, may also increase the effectiveness of treating CMV pneumonia.

Bone Marrow Transplantation↗
PubMed1989

Defective expression of basement membrane-associated C3d,g in papulonodular basal cell carcinomas.

Recent studies in our laboratory have shown that C3d,g, a 41,000-Da fragment of the third component of complement, is present along the base of the lamina densa and in the sublamina densa region of normal human epidermal basement membrane, but absent from the skin of a patient with congenital C3 deficiency. In studies of human skin, papulonodular basal cell carcinomas have served as a useful model for the investigation of various basement membrane antigens and matrix proteins. To further investigate the presence of C3d,g within epidermal basement membrane as well as examine its relationship with other known basement membrane constituents, we have analyzed serial sections of ten papulonodular basal cell carcinomas by light and immunofluorescence microscopy. In these studies, C3d,g was either absent (N = 9) or minimumly detectable (N = 1) in tumor nest basement membranes. While bullous pemphigoid and KF-1 antigens were absent (N = 6 and N = 3, respectively) or significantly decreased (N = 4 and N = 7, respectively), epidermolysis bullosa acquisita antigen was routinely present though somewhat (N = 3) or moderately decreased (N = 3). Laminin and type IV collagen were expressed normally in all tumor nest basement membranes. All constituents, including C3d,g, were present in adjacent normal epidermal basement membrane of these tumor samples. This study has demonstrated antigenic alterations within each ultrastructural subregion of papulonodular basal cell carcinoma tumor nest basement membranes by identifying the virtual absence of C3d,g (sublamina densa) as well as a significant reduction in KF-1 (lamina densa) and bullous pemphigoid (lamina lucida) antigens. Moreover, the presence of laminin, type IV collagen, and epidermolysis bullosa acquisita antigen in tumor nest basement membranes suggests that these particular constituents neither cleave C3 nor act as essential binding sites for passive incorporation of this complement component in epidermal basement membrane. These studies give additional support to the hypothesis that C3d,g is a previously unrecognized constituent of normal epidermal basement membrane and does not represent passive incorporation of circulating C3 at this site in human skin.

Adult↗
PubMed1988

Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin.

STUDY OBJECTIVE: To assess the efficacy of the combination of the antiviral agent ganciclovir (9-1,3 dihydroxy-2-propoxymethylguanine) and high-dose intravenous immune globulin for treating cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation. DESIGN: Nonrandomized prospective trial of combined treatment with two drugs; findings in these patients were compared with those in control patients treated with either of the two drugs alone. SETTING: Medical, pediatric, and intensive care units of a tertiary-care cancer treatment center. PATIENTS: Consecutive cases of 10 patients in the study group and of 11 patients in a historical control group with evidence of cytomegalovirus pneumonia after bone marrow transplantation for treatment of leukemia or congenital immune deficiency. INTERVENTIONS: Study Group (10 patients): ganciclovir, 2.5 mg/kg body weight, three times daily for 20 days, plus intravenous immune globulin, 500 mg/kg every other day for ten doses. Patients were then given ganciclovir, 5 mg/kg.d three to five times a week for 20 more doses, and intravenous immune globulin, 500 mg/kg twice a week for 8 more doses. Control Group (11 patients): ganciclovir alone (2 patients), 5 mg/kg twice a day for 14 to 21 days; cytomegalovirus hyperimmune globulin (5 patients), 400 mg/kg.d for 10 days; and intravenous immune globulin (4 patients), 400 mg/kg.d for 10 days. MEASUREMENTS AND MAIN RESULTS: Responses were observed in all patients treated with combination therapy; 7 of 10 patients were alive and well, and had no recurrence of disease at a median of 10 months after therapy. No therapeutic benefit was observed, and none of the 11 patients treated with either ganciclovir or intravenous immune globulin alone survived (P = 0.001 by Fisher exact test). CONCLUSIONS: Ganciclovir, when combined with high-dose intravenous immune globulin, appears to have significantly altered the outcome of patients with cytomegalovirus pneumonia after allogeneic bone marrow transplantation.

Acyclovir↗
PubMed1987

Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia.

Ninety-seven children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) received HLA-identical bone marrow transplants from sibling donors, after preparation with 1320 cGy of hyperfractionated total-body irradiation and high-dose cyclophosphamide. Kaplan-Meier product-limit estimates (means +/- SE) of disease-free survival at five years among patients with ALL in second remission, third remission, and fourth remission or relapse were 64 +/- 9, 42 +/- 14, and 23 +/- 11 percent, respectively, with probabilities of relapse of 13 +/- 7, 25 +/- 13, and 64 +/- 16 percent. Among patients with AML in first remission, second remission, and third remission or relapse, five-year disease-free survival estimates were 66 +/- 10, 75 +/- 15, and 33 +/- 19 percent, with respective relapse probabilities of 0, 13 +/- 12, and 67 +/- 19 percent. The most frequent cause of death in patients in early remission (ALL in second or third remission or AML in first or second remission) was bacterial sepsis, fungal sepsis, or both, most often in the presence of acute or chronic graft-versus-host disease. Among patients with ALL who received transplants while in second remission, the duration of the initial remission had no effect on the probability of relapse after transplantation. The only pretransplantation factor that significantly affected outcome was the disease status at the time of transplantation; patients in early remission had better disease-free survival. We conclude that transplantation after preparation with hyperfractionated total-body irradiation and cyclophosphamide is an effective mode of therapy in children with refractory forms of acute leukemia.

Bone Marrow Transplantation↗
PubMed1987

Selection of an intravenous immune globulin for the immunoprophylaxis of cytomegalovirus infections: an in vitro comparison of currently available and previously effective immune globulins.

In an attempt to select an i.v. immune globulin to be used for the immunoprophylaxis of cytomegalovirus (CMV) infections in recipients of allogeneic bone marrow transplants, we conducted an in vitro comparison of three newly available commercial i.v. immune globulins with two CMV hyperimmune globulin products shown to be efficacious in previous CMV immunoprophylaxis studies. We compared these products for both CMV immunoreactive antibody titer by enzyme-linked immunosorbent assay (ELISA) and for in vitro functional activity by virus neutralization using both standard laboratory and wild clinical isolates of CMV. All five products had high titers of CMV-specific IgG when assayed by ELISA, ranging from 1:1600 to 1:25,600; the two hyperimmune products had the highest titers as expected. However, both hyperimmune products, despite having much higher CMV-IgG titers by ELISA, had CMV neutralizing antibody titers only equivalent to those found in two of the three standard i.v. immune globulin products tested (mean of 1:500-1:1000). One of the three commercial immune globulins tested had a lower mean neutralizing antibody titer in lots assayed compared to the other products (mean of 1:50). There was thus no direct or predictable correlation in any of the products tested between the quantity of CMV-IgG as measured by ELISA and in vitro functional activity as measured by virus neutralization. We also noted marked variation between different lots of the same product in all three commercially available immune globulin products. To insure that both current and future CMV immunoprophylaxis trials are standardized, the quantity as well as the functional activity of CMV-specific antibodies in products used need to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1986

Trazodone-induced mania.

Two bipolar depressed patients and one unipolar depressed patient developed manic symptoms after receiving trazodone. The symptoms resolved when the treatment was discontinued or reduced. We believe the two bipolar patients are the first cases of this reaction reported in the literature.

Adult↗
PubMed1986

Rapid immunodiagnosis of cytomegalovirus pneumonia by bronchoalveolar lavage using human and murine monoclonal antibodies.

Bronchoalveolar lavage material from 54 immunocompromised patients with interstitial pneumonia was examined by immunofluorescence with cytomegalovirus-specific monoclonal antibodies. Twelve patients (22%) had cytomegalovirus detected in their lavaged cells, and 9 of these patients (17%) had proven cytomegalovirus pneumonitis. This assay detected all samples with cytomegalovirus when the virus was detected by established methods either at the time of lavage or after any other procedure in the subsequent 2 months; that is, it had a sensitivity of 100%. Cytomegalovirus could be detected within 3 hours of the lavage, and a clear correlation was seen between the number of fluorescent cells and the presence of cytomegalovirus pneumonia. All 9 patients with pneumonitis had more than 0.5% fluorescent cells, whereas the 3 patients in whom cytomegalovirus was detected without pneumonia had significantly fewer fluorescent cells. This method provides a sensitive, rapid, and quantifiable system for detection of cytomegalovirus, facilitating the early diagnosis and treatment of cytomegalovirus pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1984

A human monoclonal antibody to cytomegalovirus (CMV).

We report the development of a human monoclonal antibody to cytomegalovirus (CMV) produced from a human X human hybridoma. This hybrid was developed by fusion of an EBV-transformed cell line making antibody to CMV and a human lymphoblastoid cell line WI-L2. The antibody is directed to a CMV-specific antigen primarily in the nucleus of CMV-infected human fibroblasts. It cross-reacts with at least 10 different strains of CMV and may provide a method for the rapid in vitro diagnosis of CMV infections. The production of CMV-specific human man monoclonal antibodies from human-human hybridomas for future therapeutic use is now technically feasible with this specific method of production.

Antibodies, Monoclonal↗
PubMedDate not supplied

High dose chemotherapy with autologous peripheral blood progenitor cell transplantation in an anephric child with multiply recurrent Wilms tumor.

PURPOSE: An autologous peripheral blood progenitor cell (APBPC) transplant in an anephric child with multiply recurrent Wilms tumor using a conditioning regimen of high dose chemotherapy in conjunction with hemodialysis (HD) and peritoneal dialysis is described. PATIENT AND METHODS: The child had a left nephrectomy at 9 months of age for a stage II Wilms tumor. At 6 years of age, she required a right nephrectomy because of progressive, recurrent disease unresponsive to treatment with doxorubicin, actinomycin, and vincristine. She was maintained on peritoneal dialysis. Salvage chemotherapy consisted of 5 cycles of carboplatin and cyclophosphamide after APBPCs were collected after granulocyte colony-stimulating factor mobilization. After a preparative regimen of carboplatin, cyclophosphamide, and etoposide with closely timed HD, peripheral blood progenitor cells were infused and peritoneal dialysis was resumed. RESULTS: No nonhematopoietic toxicity occurred. Pharmacokinetic studies demonstrated that HD effectively eliminated carboplatin and provided safe, effective plasma concentrations in this anephric patient. Trilineage engraftment occurred by day +10 and the child was discharged from the hospital on day +14. She had a local recurrence on day +194 and died of progressive disease on day +660. CONCLUSIONS: With dialysis support and dose modification, high-dose chemotherapy followed by APBPC transplantation can be successfully performed in the anephric child. Given the lack of organ toxicity in this patient, increased doses of the drugs used in this preparative regimen may be possible for anephric children.

Antineoplastic Combined Chemotherapy Protocols↗