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W E Beschorner

Publications and source records attributed to W E Beschorner.

13 recordsLinked to original sources
PubMed1992

Thalidomide for the treatment of chronic graft-versus-host disease.

BACKGROUND: Allogeneic bone marrow transplantation is an accepted therapy for hematologic cancer, aplastic anemia, and inherited immunodeficiencies. Chronic graft-versus-host disease (GVHD) is the principal complication in patients surviving more than 100 days. Thalidomide has been shown experimentally to be effective in treating GVHD. METHODS: We treated 23 patients with chronic GVHD refractory to conventional treatment and 21 patients with "high-risk" chronic GVHD (identified as having at least two of the following three risk factors: chronic GVHD that has evolved from acute GVHD, lichenoid skin or mucous-membrane changes, and hepatic dysfunction. Such patients have a high mortality rate.) with thalidomide in a dose that produced a plasma level of 5 micrograms per milliliter two hours after administration. Therapy was continued for three months after a complete response or for six months after a partial response. RESULTS: The overall actuarial survival of all enrolled patients was 64 percent. Survival was 76 percent among the patients receiving salvage therapy for refractory GVHD and 48 percent among those with high-risk GVHD. A complete response was observed in 14 patients, a partial response in 12 patients, and no response in 18. Side effects were minor, most notably sedation in almost all patients. CONCLUSIONS: In this preliminary trial, thalidomide appeared to be safe and effective for the treatment of chronic GVHD. A trial comparing thalidomide with prednisone in patients with newly diagnosed chronic GVHD will be required to demonstrate its relative efficacy.

Adolescent↗
PubMed1992

t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma.

We have identified two cases of previously untreated, small lymphocytic lymphoma with extranodal involvement, which had a reciprocal translocation, t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are remarkably similar to two previously reported cases carrying this translocation with regard to clinical features, cytogenetic abnormality, histologic subtype, and immunophenotype. Molecular genetic analysis of these two cases revealed clonal gene rearrangement of the IGH locus but only germline configuration of the BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2 rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement appear to make up a phenotypically identifiable subgroup. Identification of the genes at the translocation breakpoints will be important.

Aged↗
PubMed1992

Incidental myocarditis with intravenous drug abuse: the pathology, immunopathology, and potential implications for human immunodeficiency virus-associated myocarditis.

Human immunodeficiency virus (HIV)-associated myocarditis is well reported. Many of these patients are also intravenous (IV) drug abusers. This study examined sudden death victims from the Office of the Chief Medical Examiner, State of Maryland, for active myocarditis. A group of HIV-negative drug abusers is compared with a group of HIV-negative victims without any known risk factors for the acquired immunodeficiency syndrome. Using modified Dallas criteria combined with an avidin-biotin-labeled immunoperoxidase procedure, the cases were classified as active, borderline, or absent myocarditis. Serologic analysis for circulating antimyocardial antibody was performed along with phenotypic analysis of the infiltrate. Of the 15 IV drug abuse cases examined, none were positive for HIV (enzyme-linked immunosorbent assay and Western blot). With IV drug abuse as the primary risk factor, five cases demonstrated active myocarditis, while five others had borderline myocarditis. Only one of 10 low-risk patients had a lymphocytic infiltrate consistent with borderline myocarditis. Drug abuse-related myocarditis was associated with cardiac pathology resulting in sudden death in only one case. Antimyocardial antibodies were positive in four of the 15 IV drug abuse cases, including patients with active, borderline, and absent myocarditis. The phenotypic expression of the lymphocytic infiltrates was similar to the findings reported for idiopathic and HIV-related myocarditis (Am J Pathol 137:1365-1371, 1990). Toxicology studies did not implicate any particular drug of abuse, but the increased frequency of myocarditis observed may reflect complications of cocaine or the combined effects of opiates and cocaine. Intravenous drug abuse is an independent risk factor for myocarditis and must be taken into consideration in studies of HIV-associated myocarditis.

Adult↗
PubMed1992

In situ detection of human cytomegalovirus immediate-early gene transcripts within cardiac myocytes of patients with HIV-associated cardiomyopathy.

OBJECTIVE: Recent clinical and echocardiographic studies have identified dilated cardiomyopathy in 10-20% of HIV-infected adults. The purpose of this study was to determine the role of cardiotropic cytomegalovirus (CMV) infection in the development of HIV-associated cardiomyopathy. DESIGN: We generated sense and antisense digoxigenin-labeled riboprobes derived from the CMV immediate-early (IE) and delayed-early (DE) genes and applied them retrospectively to endomyocardial biopsy samples and control autopsy cardiac samples from HIV-infected patients. SETTING: Tertiary care, referral hospital. PATIENTS: Twelve consecutive HIV-infected patients with global left ventricular hypokinesis demonstrated on two-dimensional echocardiography; eight randomly selected control autopsy cardiac samples from HIV-infected patients without cardiac disease during life. MEASUREMENTS AND MAIN RESULTS: Of the 12 endomyocardial biopsy specimens, six (50%) were found to have specific myocyte nuclear and perinuclear hybridization for transcripts of the CMV IE gene, consistent with non-permissive or latent infection. Similar patterns were not found in any of the eight autopsy control samples. All six patients presented with unexplained congestive heart failure and had CD4 counts less than 100 x 10(6)/l; all six biopsy samples had immunohistochemical evidence of increased myocardial major histocompatibility complex (MHC) class I expression, a finding typical of non-HIV myocarditis. None of the endomyocardial biopsy samples had characteristic CMV inclusions and no specific hybridization was noted with the DE gene riboprobe, suggesting that no active viral DNA replication was present. Only two of the six patients with myocyte hybridization with the IE riboprobe had clinical evidence of solid organ infection with CMV at the time of cardiovascular presentation. CONCLUSIONS: This study is the first to demonstrate the expression of the IE gene of CMV within myocytes from HIV-infected patients with cardiomyopathy, suggesting a non-permissive infection of myocytes without classical intranuclear inclusions. Myocyte infection may be necessary to trigger cellular and humoral-mediated cardiac injury and may be best identified using in situ hybridization techniques.

Adult↗
PubMed1992

Graft-specific MHC class II gene expression in response to allogeneic stimulus in heterotopic murine cardiac allografts.

Although, major histocompatibility complex (MHC) class II antigen expression in allografts is thoroughly studied, regulation of the genes for these antigens is not fully understood. The graft-specific MHC class II genes are potentially important in determining the immunogenicity of graft but their detection in a mixed-cell population such as in the allograft would require unambiguous differentiation of graft-specific class II expression from those in host lymphoid cells. With an oligonucleotide probe that specifically hybridizes to I-Ab mRNA from H-2k haplotype mice, we have studied I-A gene expression in cardiac allografts heterotopically transplanted from B10.Br (H-2k) to B10.D2 (H-2d) mice. Normal B10.Br hearts do not have appreciable I-Ab transcripts as determined with this probe, but 4 days after allografting, a substantial increase in I-Abk messenger RNA (mRNA) content was noted in the allografted hearts which persisted for the next 2 days and then decreased concomitant with destruction of the heart. The increase in I-Abk mRNA preceded the expression of surface Iak antigens on dendritic and endothelial cells in the allograft. These data indicate increased transcription of the I-Ab gene in cells of graft origin suggesting that transcriptional regulation is the initial mechanism for expression of class II genes in allografts. The sustained rise in graft-specific class II mRNA also seen in these allografts suggests that increased mRNA stability may be another mechanism for the increased density of class II antigens in allografts undergoing rejection.

Animals↗
PubMed1991

Prominent mononuclear cell infiltrate is characteristic of herpes esophagitis.

Diagnosis of herpes esophagitis is often difficult since the characteristic nuclear inclusions and/or multinucleate giant cells of herpes virus infection may be absent in endoscopic biopsy specimens. We have noted aggregates of large mononuclear cells with convoluted nuclei adjacent to infected epithelium in the exudates of herpetic esophagitis, and postulate that this is a characteristic inflammatory response to the virus. To test this hypothesis, we reviewed biopsies from 22 cases of ulcerative herpetic esophagitis and from 44 control cases of nonherpetic esophageal ulcers (including nine cases of candidal and five cases of bacterial esophagitis) that contained a quantifiable amount of exudate. The estimated percentage of mononuclear cells present in the specimens was ranked independently by two reviewers using coded photomicrographs of exudate. Wilcoxon's rank sum analysis demonstrated significant correlation between presence of herpes and increased mononuclear cells (P less than .0001). Only one of the 22 herpes cases did not show a prominent mononuclear cell infiltrate. Immunoperoxidase studies performed on Hollande-Bouin's-fixed paraffin-embedded material from 11 herpes cases showed strong staining of the mononuclear cells for KP-1 (CD68), indicating that the majority of these cells are macrophages. These findings suggest strongly that aggregates of macrophages are characteristic of the inflammatory response in ulcerative herpetic esophagitis. The presence of these mononuclear cells in a biopsy specimen that initially does not show herpetic inclusions warrants additional studies to rule out herpes virus infection.

Adolescent↗
PubMed1990

Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis.

Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.

Adult↗
PubMed1979

Pulmonary interstitial changes following bone marrow transplantation.

Observations of 20 consecutive bone marrow transplantation recipients disclosed two distinctive categories of pulmonary interstitial changes. Interstitial infiltrates occurring less than 14 days after transplantation were observed in 13 of 20 patients and are believed to represent pulmonary edema. A late pulmonary interstitial process, which appears more than 30 days following transplantation (median 57 days), was encountered in 10 of 14 patients with successful grafts; the late changes represent interstitial pneumonia, a common cause of morbidity and mortality following bone marrow transplantation. It is probably attributable to a combination of factors including the preparatory chemotherapy and radiotherapy, and delayed immunologic reconstitution following transplantation.

Adult↗
PubMed1979

Isolation and characterization of canine venereal tumor-associated inhibitory and blocking factors.

Spontaneous regression of the canine venereal tumor is associated with the production of a serum factor which inhibits in vitro tumor colony-forming units in agar. Logarithmic or persistent tumor growth, on the other hand, is characterized by a serum factor which protects cells against in vitro inhibition (blocking factor). These factors have been characterized by immunochemical methods. Whole regressor and blocking sera were fractionated by Sephadex G-200 filtration and immunoabsorption with rabbit antiserum specific for canine immunoglobulin G2a. Fractions were characterized by immunoelectrophoresis, radial immunodiffusion, and disc gel electrophoresis. In vitro inhibitory and blocking activity of the whole serum was accounted for by the purified immunoglobulin G2a. Blocking activity was also found in protein eluted from logarithmically growing tumors. Preparative polyacrylamide electrophoresis revealed five major fractions with blocking activity only in the immunoglobulin G fraction. Tumor eluates and immunoglobulin G isolated from serially removed tumors demonstrated with the clinical course of the tumor. Using ultrafiltration and sodium dodecyl sulfate electrophoresis of tumor-associated immunoglobulin G at low pH, it was not possible to identify an antigen complexed to the blocking antibody.

Animals↗
PubMed1978

Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants.

Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.

Adolescent↗
PubMed1978

The thymus in patients with allogeneic bone marrow transplants.

The thymus glands from 11 patients with aplastic anemia or acute leukemia who received allogeneic bone marrow transplants were studied at autopsy. All showed marked cortical involution. In the short-term survivors the medulla and perivascular spaces were lymphocyte-depleted and the epithelial cells formed pseudorosettes. In those surviving over 2 months, increasing numbers of small lymphocytes were present, presumably reconstituted with donor lymphocytes. Phagocytosis of cellular debris was frequent, especially in patients with graft-versus-host reaction (GVHR) or treated with anithymocyte globulin (ATG). Plasma cells were numerous in perilobular tissue and were occasionally found within the medulla. The findings are compatible with the concept that the thymus plays an important role in the immune deficiency experienced after allogeneic bone marrow transplantation and in the subsequent lymphoid reconstitution.

Adolescent↗