PubMed Health⌕ Search

Biomedical subjects

S C Springmeyer

Publications and source records attributed to S C Springmeyer.

29 records · Page 2Linked to original sources

Treatment of cytomegaloviral pneumonia with high-dose acyclovir and human leukocyte interferon.

Thirteen recipients of bone marrow transplants were given high-dose acyclovir and alpha-interferon (Cantell interferon) for the treatment of biopsy-proven cytomegaloviral pneumonia. Three patients survived. Doses of acyclovir between 500 and 1,000 mg/m2 of body surface area (peak plasma levels, 7-86 micrograms/ml) and doses of interferon between 2 X 10(4) and 40 X 10(4) units/kg per day (peak serum levels, 5-608 units/ml) were given. No consistent antiviral effect was seen despite the large doses employed. Possible marrow toxicity associated with this regimen occurred in five patients, neurologic symptoms in two, and nephrotoxicity in one. Thus, treatment with high-dose acyclovir plus alpha-interferon was moderately toxic but ineffective against cytomegaloviral pneumonia after bone marrow transplantation.

Acyclovir↗

The use of acyclovir for cytomegalovirus infections in the immunocompromised host.

Despite the lack of virus-specified thymidine kinase activity, human cytomegalovirus may be sensitive to acyclovir in vitro at concentrations between 10 and 25 mg/l. The inhibitory effect of acyclovir can be further increased by the presence of small amounts of human alpha or beta interferon. Twenty-one allogeneic marrow graft recipients with biopsy-proven cytomegalovirus pneumonia were treated with either high doses of acyclovir (eight patients) or the combination of acyclovir and human alpha (leukocyte) interferon (13 patients). Acyclovir doses of 400 to 1200 mg/m2/dose and interferon doses of 2 to 40 X 10(4) units/kg/day were used. There was no consistent effect of treatment on the likelihood or duration of survival, titre of virus in paired lung specimens, or shedding of virus. However, four patients survived and four others had 2-log or greater decreases in the amount of virus in paired lung specimens, suggesting a possible effect on cytomegalovirus strains with increased sensitivity to these agents. Acyclovir treatment of cytomegalovirus infection may be more effective in patients with lesser degrees of immunosuppression, but was not effective in the treatment of marrow transplant patients with cytomegalovirus pneumonia.

Acyclovir↗

Mycobacterial infections in marrow transplant patients.

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

Adolescent↗

Treatment of cytomegalovirus pneumonia with high-dose acyclovir.

Cytomegalovirus pneumonia is a serious complication of marrow transplantation, with a 90 percent fatality rate. Acyclovir, a new antiviral agent with variable in vitro activity against cytomegalovirus, was administered to eight marrow transplant patients with biopsy-proven cytomegalovirus pneumonia; one patient survived. Doses were between 400 and 1200 mg/m2 and peak plasma levels between 47 and 316 microM were attained. Possible marrow toxicity occurred in three patients, and mild neurotoxicity occurred in one. High-dose acyclovir had mild toxicity but was not effective as treatment for cytomegalovirus pneumonia after marrow transplantation.

Acyclovir↗

Unusual distribution of Ia-like antigens on canine lymphocytes.

The murine monoclonal antibody 7.2, specific for a framework determinant of human Ia antigens, cross-reacts with canine cell membranes recognizing a bimolecular complex (29,000 and 34,000 daltons) similar to that described in man. We investigated the distribution of these Ia-like antigens on mononuclear cells in peripheral blood, thoracic-duct lymph, marrow, alveolar lavage fluids, lymph nodes, and thymuses from normal dogs. By complement-mediated cytotoxicity and indirect immunofluorescence, virtually all lymphocytes expressing surface immunoglobulin (B lymphocytes), monocytes/macrophages, dendritic cells, and many thymus-epithelial cells were Ia-positive. Furthermore, most non-B-lymphocytes in peripheral blood, thoracic-duct lymph, and lymph nodes expressed Ia antigens. Alveolar (T) lymphocytes and most thymocytes were Ia-negative. Generally, fluorescence intensity was higher on monocytes/macrophages and B lymphocytes than on non-B-lymphocytes. In mixed leukocyte cultures and concanavalin A-induced blastogenesis assays, treatment of responder cells with antibody 7.2 and complement abolished proliferation. Proliferative responses could not be restored by adding untreated accessory cells, indicating that cytolytic treatment had eliminated responder T-lymphocytes. However, addition of antibody alone to cultures had no significant effect. These studies indicate that most mature canine T-lymphocytes express Ia-like antigens. Whether this is an intrinsic property of canine cells or possibly related to continuous in vivo stimulation remains to be determined.

Animals↗

Alveolar macrophage kinetics and function after interruption of canine marrow function.

To study the kinetics and function of alveolar macrophages after interruption of marrow function, we performed serial bronchoalveolar lavages in dogs. The studies were performed before and after 9.0 to 9.5 Grey total body irradiation and marrow infusion. Monocytes had disappeared from the bloodstream by Day 7 after the irradiation. Alveolar macrophages were significantly decreased at Day 21. At Days 14 and 21 myeloperoxidase-positive alveolar macrophages were also significantly decreased. Beyond Day 30 the number of circulating monocytes, myeloperoxidase-positive and total alveolar macrophages had returned. Sex chromatin stains of alveolar macrophages obtained from a male dog that received female marrow indicated that the repopulating macrophages were of marrow origin. In vitro studies of alveolar macrophage migration and phagocytosis demonstrated increased activities beyond Day 30. These studies suggest that in this model the alveolar macrophage is dependent on the bone marrow for support and that the alveolar macrophage depletion may impair lung defense mechanisms.

Animals↗

The role of transbronchial biopsy for the diagnosis of diffuse pneumonias in immunocompromised marrow transplant recipients.

We studied the use of transbronchial biopsy for the diagnosis of diffuse pneumonia in marrow transplant recipients. Transbronchial biopsy results were directly compared with open-lung biopsy results by performing the procedures simultaneously in the same lobe of the lung and processing the specimens in parallel. There were 24 cases of pneumonia diagnosed in 22 patients. Transbronchial biopsy correctly identified 3 of 5 cases of Pneumocystis carinii and none of the 5 cases of viral pneumonia. The overall sensitivity of transbronchial biopsy was 58%, with a 13% incidence of moderate hemorrhage and no deaths. We conclude that the open-lung biopsy remains the procedure of choice for the diagnosis of acute, diffuse pneumonia in the immunocompromised marrow transplant recipient.

Biopsy↗

Two monoclonal antibodies (DLy-1 and DLy-6) directed against canine lymphocytes.

Two murine monoclonal antibodies directed against canine lymphocytes are described. DLy-1, raised against puppy thymocytes, and DLy-6, raised against bronchoalveolar lymphocytes, both react with most lymphocytes in peripheral blood, thoracic duct lymph, and bronchoalveolar lavage fluids. DLy-1 also recognizes monocytes and granulocytes. However, it is not reactive with erythrocytes, megakaryocytes, or platelets. Expression of DLy-1 antigen on thymocytes ranged from 5--30%. The distribution of DLy-6 antigens seems to be confined to lymphoid cells. Ten to 60% puppy thymocytes were positive. Interestingly, lymphoblasts formed in response to stimulation with mitogens or alloantigens lacked DLy-6 in contrast to DLy-1 cell surface antigen expression.

Animals↗

Invasive aspergillosis presenting as pericarditis and cardiac tamponade.

A 38-year-old leukemic patient developed pericarditis and cardiac tamponade due to Aspergillus niger one month after undergoing bone marrow transplantation. She failed to improve even though amphotericin B and rifampin therapy had been initiated before infection was evident. Her unique case illustrates both the unusual presentations of invasive aspergillosis and the difficulty of diagnosing and treating this increasingly common disease.

Adult↗

TCR expression and clonality analysis in pulmonary sarcoidosis.

Pulmonary sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lower respiratory tract. To evaluate the hypothesis that sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR)-specific T cells, we analyzed TCRAV and TCRBV gene expression in bronchoalveolar lavage (BAL) T cells from sarcoidosis patients and, for comparison, from patients with other pulmonary diseases where lymphocyte accumulation is not observed. Increased expression of TCRAV9 and TCRAV14 in BAL T cells was observed in sarcoidosis patients compared to these controls. To ascertain whether the accumulation of AV9 and AV14 expressing BAL T cells in sarcoidosis was the result of clonal expansion, the lengths of the CDR3 regions in AV9 and AV14 transcripts were determined. Some individual patient samples showed evidence of oligoclonality. However, in most cases, the data were consistent with the presence of many different clones. These data suggest that the bulk of BAL T cells in sarcoid patients are either nonspecifically recruited or are responding to a complex mixture of antigens.

Bronchoalveolar Lavage Fluid↗