Cytomegalovirus infection in marrow transplantation.
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Antiviral Agents↗
Biomedical subjects
R Bowden
Publications and source records attributed to R Bowden.
Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features.
To determine the prevalence of fungal liver infection at autopsy in marrow transplant recipients, we reviewed autopsy results for the period 1980-1989. Cases were compared to randomly chosen autopsied controls without fungal infection. Fungal liver infection was found in 67 (9%) of 731 patients. Fungal cultures of liver lesions were positive for 34 of 67 patients, most of whom had been culture-positive for the same fungal species (largely Candida) during life. Multivariate analysis revealed that independent predictors of fungal liver infection were deep fungal infection after transplantation (RR, 35), colonization or superficial infection after transplantation (RR, 13), and severe liver dysfunction caused by veno-occlusive disease of the liver and/or graft-versus-host disease (RR, 7). Clinical and laboratory findings during the last month of life revealed no differences between cases and controls. Liver imaging studies performed during the last 15 days of life had a sensitivity of only 18% for detecting fungal liver lesions.
Adult↗
Marrow transplantation for patients in accelerated phase of chronic myeloid leukemia.
The records were reviewed of 58 patients receiving transplants in Seattle with unmanipulated marrow from HLA-identical siblings during the accelerated phase (AP) of chronic myeloid leukemia. Variables examined for association with survival and relapse included the interval from diagnosis to transplant, the reasons for categorization as AP, age, regimen, and cytomegalovirus serology. Four patients relapsed. The 4-year probabilities of survival, relapse-free survival, nonrelapse mortality, and relapse were 0.49, 0.43, 0.51, and 0.12, respectively. After completion of the stepwise multivariate analysis, age less than 38 years and categorization as AP solely on the basis of chromosomal abnormalities emerged as being independently significantly associated with improved survival. The 4-year probability of survival for the 16 patients categorized as AP because of chromosomal abnormalities and receiving transplant less than 1 year from diagnosis was 0.74. The low probability of relapse in these patients suggests that more aggressive preparative regimens are not indicated for patients receiving transplants in AP because of the increased risk of transplant-related mortality.
Acute Disease↗
Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide.
A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.
Adolescent↗
Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention.
One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.
Anemia, Aplastic↗
Strategies for the prevention of cytomegalovirus disease after marrow transplantation.
The purposes of this review are to examine the epidemiology of disease due to cytomegalovirus (CMV) in recipients of autologous and allogeneic marrow transplants and to compare different antiviral regimens used for the prevention of such disease in recipients of allogeneic marrow transplants, with an emphasis on ganciclovir. In seven studies, ganciclovir reduced the incidence of CMV infection and disease after allogeneic marrow transplantation. In one study mortality after transplantation was reduced because of a decreased rate of CMV-related death among ganciclovir-treated patients. Ganciclovir was effective when given to all CMV-seropositive patients (prophylaxis) or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture (early treatment). The effectiveness of ganciclovir for the prevention of CMV infection and disease is limited by drug-induced neutropenia. Experience with other antiviral agents, such as foscarnet, has been limited. Initial studies of the adoptive transfer of CMV-specific CD8+ cytotoxic T cells have been conducted. In short, ganciclovir is currently effective for the prevention of CMV disease in allogeneic marrow transplant recipients, but its usefulness is limited by neutropenia. Future studies must be aimed at confining the toxicity of ganciclovir to patients at the highest risk for CMV disease.
Bone Marrow Transplantation↗
Cytomegalovirus infection of the tongue following marrow transplantation.
Tongue ulcerations in seven patients who had undergone allogeneic BMT for hematologic or lymphoid malignancies were examined for the presence of CMV. The clinical presentation of these tongue lesions was nonspecific and showed ulcerations similar to those associated with severe preparative conditioning regimen-related mucositis, HSV infection and oral acute GVHD. Tissue biopsies were studied by routine histology, immunocytochemistry for CMV and HSV antigens, in situ hybridization for CMV nucleic acid and standard as well as centrifugation viral cultures. Five of the 7 patients had lesions which were positive for CMV. While CMV oral lesions are known to occur in patients with the acquired immune deficiency syndrome (AIDS), these findings will improve our ability to recognize and diagnose tongue lesions in BMT patients and indicate that CMV should be considered in the differential diagnosis for similar ulcerations in other immunocompromised patients.
Adult↗
Late complications of allogeneic and autologous marrow transplantation.
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Bone Marrow Transplantation↗
Protection conferred on mice by monoclonal antibodies directed against outer-membrane-protein antigens of Brucella.
Twenty-six monoclonal antibodies (MAbs) directed against seven brucella outer-membrane proteins (OMPs) of 10, 16.5, 19, 25-27, 31-34, 36-38 and 89 Kda were screened for passive protection of mice; three MAbs (directed against 16.5, 25-27 and 36-38 Kda) reduced significantly the initial colonisation of the spleen measured 7 days after challenge. Although significant, the reduction in numbers of Brucella organisms in the spleen was low compared with that conferred by MAbs against lipopolysaccharide of smooth specificity (S-LPS). The three most protective MAbs belonged to two isotypes (IgG1 and IgG2a) and were specific for three different OMPs. No relationship between protection and binding of MAbs to the challenge S strain or its rough mutant was observed in the mouse model. The humoral protection depended mainly on antibodies directed against S-LPS, although some MAbs against OMPs had weak protective activity.
Animals↗
Chronic fatigue. A prospective clinical and virologic study.
To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.
Adult↗
Supportive care of the marrow transplant recipient: the Seattle Experience.
It is now almost 2 decades after the first successful human marrow transplants from HLA-identical siblings for the treatment of life-threatening hematologic diseases. Results have improved, especially for patients transplanted earlier in the course of disease. However, major problems remain in supporting patients through the transplant. More effective and less toxic conditioning regimens are needed. Acceleration of hematopoietic and immunologic reconstitution by use of various cytokines holds promise for decreasing infectious morbidity and mortality. Improved regimens to control acute and chronic GVHD and prevent opportunistic infections will play a major role in the advancement of supportive care of the marrow transplant recipient.
Anti-Infective Agents↗
The risk of transmitting cytomegalovirus infection by fresh frozen plasma.
In order to determine if cytomegalovirus seronegative patients are at risk of infection from fresh frozen plasma we reviewed our experience with 21 seronegative marrow transplant recipients who underwent plasma exchange with unscreened plasma. The mean (+/- SD) number of units of plasma required in the procedure was 47.6 (+/- 19.5). The majority of patients, 17 of 21, were followed for 100 days. No patients had evidence of cytomegaloviral infection. We conclude that fresh frozen plasma is not infectious for cytomegalovirus.
Cytomegalovirus Infections↗
Anal human papillomavirus infection among human immunodeficiency virus-seropositive and -seronegative men.
Homosexual men are at high risk of anorectal human papillomavirus (HPV) infection, HPV-related anal cancer, and precancer, conditions known to increase with immunosuppression. The relationship between anal HPV infection, human immunodeficiency virus (HIV) infection, and immunosuppression was studied in homosexual men seen at a sexually transmitted disease clinic. History or presence of warts on rectal examination, and detection of anorectal HPV DNA were each significantly associated with HIV seropositivity after adjusting for age, previous sexual behavior, and cultural or serologic evidence of other sexually transmitted diseases, including those previously identified as risk factors for acquisition of HIV infection. Decreased mean levels of T4 lymphocytes were significantly associated with the detection of anal HPV DNA. Prospective studies are needed to determine incidences of anal HPV infection and cancer among HIV-seropositive and -seronegative mean and to determine the temporal relationship of these infections to one another.
Anus Diseases↗
Endogenous IFN-gamma during human bone marrow transplantation. Analysis of serum levels of interferon and interferon-dependent secondary messages.
Serum levels of interferon-gamma and the IFN-dependent marker molecules neopterin and beta 2-microglobulin were assessed in BMT recipients. Concentrations of the latter two markers were corrected for creatinine levels in order to eliminate the impact of alteration of kidney function. Serum levels were assessed daily using commercially available radioimmunoassays. Twelve patients were studied during the early phase of allogeneic bone marrow transplantation and eleven additional patients during complications of BMT. Results indicated that both the conditioning regimen for BMT as well as major clinical complications such as infection and acute graft-versus-host disease strongly influence the endogenous patterns of the lymphokine and its secondary messages. During allogeneic BMT IFN-gamma and neopterin levels exhibited a biphasic pattern with a first peak during conditioning with high-dose cyclophosphamide and a second still higher peak at the time of hemopoietic regeneration. beta-2-microglobulin ratios increased during conditioning and remained elevated throughout observation. Serious infections of bacterial and viral origin as well as GvHD were accompanied by elevated levels of all three serum parameters studied. The kinetics of enhanced endogenous production, however, differed between infectious complications and GvHD. Increasing concentrations were observed during infections subsequent to clinical manifestation, whereas they preceded disease manifestation in GvHD.
Biopterins↗
Cell volume alterations induced by platinum-thymine in sarcoma-180 ascites cells: ultrastructural study.
Ultrastructural studies of the effects of the chemotherapeutic agent platinum-thymine, on the morphology of sarcoma-180 ascites cells were studied to elucidate the cancer cells immediate response to therapy and the possible mode of cancer cell regression. Sarcoma-180 ascites cells treated with platinum-thymine in vitro at concentrations of 60 micrograms/ml at varying time intervals demonstrated that the drug is capable of killing cancer cells. The cells exhibited drastic nuclear and cytoplasmic alterations with few lipid spherules in the cytoplasm. The cell volume increased tremendously, with the nucleus relatively larger than the cytoplasm as time of treatment increased. Degradative features of the nucleus, and especially the nucleolus, inhibited metabolic processes. Nucleolar and cytoplasmic necrosis with increased cell volume and vacuolation are potential signals for cancer cells response to the drug and a possible mode of causing the eventual demise of the cancer cells.
Animals↗
Effects of platinum-thymine on mitosis of sarcoma-180 ascites cells in vitro: ultrastructural study.
Electron microscopic studies of sarcoma-180 ascites cells, which were treated with platinum-thymine at a concentration of 60 micrograms/ml, showed mitotic inhibition. The drug clumped the chromosomes into a compact mass at the center of the cell preventing them from separating during mitosis. Prolonged treatment depolymerized spindle fibers and cytoplasmic microfilament. Degraded cytoplasmic organelles crowded around the clumped chromosomes. Disintegrating and casting off of cortical cytoplasm was apparent. Platinum-thymine-treated cells did not resume mitosis irrespective of the amount of time they were allowed to remain in fresh medium. Perturbation of mitotic machinery by platinum-thymine inhibited the mitotic process and caused eventual demise of the cancer cells.
Animals↗
Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity.
A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia. Only five of the 50 serum samples had INF-gamma levels above background (greater than 0 less than 0.5 units per mL). Detectable levels of spontaneous INF-gamma (0.3 to 868 U/mL) were found in 18 of the 50 mononuclear cell supernatants tested. The addition of patient sera or INF-gamma positive supernatants to cultures of normal hematopoietic colonies did not result in reduced colony growth. Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF-gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population. However, a significant correlation did exist between the presence of monocytes and the production of INF-gamma. Contrary to previous reports, our data suggest that patients with aplastic anemia do not have high circulating levels of INF-gamma. Unstimulated mononuclear cells from some patients will produce significant levels of INF-gamma, but this does not result in decreased in vitro hematopoiesis.
Anemia, Aplastic↗
Computerization of undergraduate medical curriculum content.
A method is reported for the computerized storage and retrieval of informative summaries of the didactic portion of the first 3 years of the medical undergraduate curriculum utilizing the MICOM word processor and SORT 200 program with disc storage. Each lecture, small group session, laboratory or clinical experience summary is assigned a page of computer memory and is coded in the header line for various indices describing the session format, location, audiovisual usage, teacher and other demographics. The second line contains the lecture title and its situation within the teaching block. A summary of the teaching session follows. This was compiled and distilled from summaries prepared by the individual teachers, lecture handouts and the personal notes of the two medical students who divided the lectures equally between themselves and prepared individual summaries which were then exchanged. The resulting composite summary was returned to the teacher for comment and/or modification before entry onto the MICOM word processor. The SORT 2000 program permits search, selection and retrieval of the content of each teaching session from the data contained in the header line or any word, word segment or phase occurring in the summary. Reproduction of the data discs facilitates multiple access and allows each department or teaching block to review the complete curriculum quickly, identify redundancies and more fully integrate new or existing material.
Computers↗