Biomedical subjects

R B Mann

Publications and source records attributed to R B Mann.

At least 55 records · Page 3Linked to original sources

PubMed1991

Stereotactic brain biopsy in the diagnosis of malignant lymphoma.

Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically.

Adolescent↗

PubMed1991

Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease.

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.

Adult↗

PubMed1991

Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens.

The highly restricted expression of the Epstein-Barr virus (EBV) genome in malignancy has limited the use of EBV detection methods applicable to formalin-fixed paraffin-embedded carcinoma specimens. In EBV-transformed lymphocytes very short nonprotein coding EBV transcripts (EBERs) are expressed in much higher abundance (10(7) copies per cell) than other EBV latency transcripts. Using a 3H riboprobe, the authors demonstrated EBER1 expression in NASOPHARYNGEAL CARCINOMAS (NPCs) as well as in parotid salivary gland. Recognition of EBER1 expression was facilitated by the intensity of hybridization and its characteristic morphology (nuclear with nucleolar sparing). EBER1 expression was not demonstrated in other epithelial malignancies arising from mucosal surfaces (oropharynx, uterine cervix) from which EBV shedding has been detected. Repeat study of the NPC specimens with digoxigenin-labeled probe yielded hybridization signal with subcellular morphologic detail and without background in a 12-hour procedure. Thus the EBER1 transcript is an appropriate target for in situ hybridization detection of EBV in formalin-fixed paraffin-embedded carcinoma specimens.

Carcinoma↗

PubMed1991

Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition.

The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced.

Coronary Disease↗

PubMed1990

Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease.

EBV DNA has been detected by Southern blot hybridization in 20-25% of Hodgkin's disease tumor specimens and localized to the Reed-Sternberg cells by in situ hybridization. In the present investigation we used a 3H-labelled EBER I anti-sense RNA for in situ hybridization of archival formalin-fixed paraffin-embedded Hodgkin's disease specimens previously shown by Southern Blot hybridization to be EBV-positive. In 6 of 8 specimens neoplastic cells showed an intense signal in virtually all of the tumor cells. The background lymphocytes, eosinophils, plasma cells and histiocytes did not demonstrate significant hybridization. In each case hybridization tended to spare the nucleoli. Hybridization was detected in specimens with histologies of mixed cellularity and nodular sclerosis. The intensity of signal relative to background is better than that in previous studies utilizing 35S-labelled large internal repeat probes for EBV in Reed-Sternberg cells. The exposure time is one week in contrast to the 4-5 weeks reported by others for detection of EBV in Hodgkin's disease. Both increased relative intensity and shorter exposure requirements may be attributed to the very high number of EBER transcripts in the target cells. The demonstration that EBER I is expressed is consistent with a role for EBV in growth regulation of Reed-Sternberg cells and suggests that the virus is not merely a silent passenger in Hodgkin's disease.

Blotting, Southern↗

PubMed1990

Oligonucleotides for polymerase chain reaction amplification and hybridization detection of Epstein-Barr virus DNA in clinical specimens.

We designed synthetic oligonucleotide primers and hybridization probe for use in polymerase chain reaction (PCR) amplification and hybridization detection of Epstein-Barr virus (EBV) nucleic acid sequences. Primer sequences were chosen from the coding region for the Epstein-Barr virus nuclear antigen-1 (EBNA-1). PCR amplification and hybridization with these oligonucleotides was carried out on standard laboratory cell lines including African Burkitt's lymphoma and infectious mononucleosis derived cell lines, as well as cell lines recently established from clinical EBV isolates from bone marrow transplant recipients. All EBV cell lines tested were positive. No false-positives were detected with uninfected cell lines, human placental DNA or with other viruses. The sensitivity of the detection procedure was such that four copies of the EBV genome could consistently be detected in a background of 1 microgram of placental DNA. EBV was detected in DNA extracts from the peripheral blood mononuclear cells of two patients with infectious mononucleosis and one patient with viral-associated hemophagocytic syndrome. Three of 18 EBV seropositive patients without known ongoing EBV-associated illness undergoing ambulatory surgery also had EBV detected in DNA extracts from their peripheral blood mononuclear cells. EBV was detected in DNA extracts from lymphoma tissue from two patients with post-transplant lymphomas and two AIDS patients with primary CNS lymphomas. EBV was not detected in 12 B-cell lymphoma specimens from patients without history of immunocompromise. DNA extracts from formalin-fixed paraffin-embedded Hodgkin's tissues previously shown to be EBV positive by Southern blot were also demonstrated to be EBV positive by PCR. Thus, with the oligonucleotides described, PCR is applicable to the detection of EBV in a spectrum of clinical isolates. The broad specificity of these oligonucleotides for all strains of EBV tested is probably a function of the highly conserved sequence of the EBNA-1 DNA binding domain.

Antigens, Viral↗

PubMed1990

High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease.

Patients with Hodgkin's disease who have failed two or more chemotherapy regimens or who have relapsed after an initial chemotherapy-induced remission of less than 12 months are seldom cured with conventional salvage therapies. We studied the effect of high-dose cytoreductive therapy followed by bone marrow transplantation in 50 such patients with relapsed Hodgkin's disease. Twenty-one patients with histocompatibility locus antigen (HLA)-matched donors had allogeneic marrow transplants, one patient received marrow from an identical twin, and 28 patients without a matched donor received autologous grafts purged with 4-hydroperoxycyclophosphamide. Busulfan plus cyclophosphamide was the preparative regimen for the 25 patients who had received extensive prior irradiation, and the other 25 patients received cyclophosphamide plus total body irradiation. The overall actuarial probability of event-free survival at 3 years was 30%, with a median follow-up of 26 months. The event-free survival following transplantation was influenced by the number of chemotherapy failures and the patient's response to conventional salvage therapy prior to transplant. The 16 patients who were transplanted at first relapse, while still responsive to standard therapy, had a 64% actuarial probability of event-free survival at 3 years. Age, presence of extranodal disease, preparative regimen, and type of graft (autologous v allogeneic) were not significant prognostic factors. The majority of transplant-related deaths were from interstitial pneumonitis; inadequate pulmonary function, multiple prior chemotherapy regimens, and prior chest irradiation all appeared to increase the transplant-related mortality. These results suggest a role for marrow transplantation in a subset of patients with relapsed Hodgkin's disease who are unlikely to be otherwise cured but are still responsive to conventional-dose cytoreductive therapy.

Actuarial Analysis↗

PubMed1989

Induction of graft-versus-host disease after autologous bone marrow transplantation.

To induce graft-versus-host disease (GvHD) in patients undergoing autologous bone marrow transplantation (BMT), five consecutive patients with non-Hodgkin lymphoma or Hodgkin's disease in resistant relapse were treated with cyclophosphamide and total body irradiation or busulphan and cyclophosphamide, followed by autologous BMT. The patients received cyclosporin 1 mg/kg per day intravenously for 28 days after BMT. Histologically proven grade II acute GvHD of the skin developed in all the patients at a median of 11 days (range 9-13) after BMT. One patient died and the GvHD resolved in 1-3 weeks in the four remaining patients--spontaneously in two and with corticosteroid treatment in two. Lymphocytes from one patient obtained at the time of GvHD were cytotoxic for the patient's own pretransplant lymphocytes. Cytotoxicity was blocked by antibodies directed against class II histocompatibility (HLA-DR or Ia) antigens. Cyclosporin-induced GvHD after autologous BMT resembles mild GvHD after allogeneic grafting. This syndrome appears to be mediated by autoreactive Ia-specific lymphocytes.

Acute Disease↗

PubMed1988

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Clinical Trials as Topic↗

PubMed1988

Splenic hematopoiesis in polycythemia vera. A morphologic and immunohistologic study.

Spleens from 42 patients with polycythemia vera were studied with immunohistologic technics to assess the degree of hematopoietic cellularity in an attempt to clarify the pathogenesis of the splenomegaly characteristic of this disorder. The 22 spleens obtained in the erythrocytotic phase showed striking congestion with mature erythrocytes but no significant extramedullary hematopoiesis. However, the 20 spleens obtained in the spent phase showed prominent trilinear extramedullary hematopoiesis. Increasing splenomegaly with extramedullary hematopoiesis correlated with the development of increased medullary reticulin and peripheral blood leukoerythroblastosis. Splenic myeloid metaplasia is not a feature of uncomplicated polycythemia vera, and its presence indicates progression to the spent phase, or postpolycythemic myeloid metaplasia. The authors' findings indicate that the presence of hematopoietic precursors in the spleen in the spent phase of polycythemia vera and in agnogenic myeloid metaplasia is a result of their filtration from the peripheral blood.

Adult↗

PubMed1987

Mitotic counts in follicular lymphomas.

Increased mitotic activity is associated with significantly shorter patient survival in some of the subtypes of diffuse non-Hodgkin's lymphomas. This study on 105 cases of follicular lymphoma was undertaken to determine the clinical significance of mitotic activity in follicular lymphomas. For each case, two pathologists independently counted mitotic figures in 20 random high-power fields. The difference of the average mitotic counts over 20 high-power fields for the two pathologists showed a Gaussian distribution with a median difference of -0.26 counts per high-power field and a standard error of 0.10 per cent. In 94 cases (91 per cent), the difference was less than two mitotic counts per high-power field, indicating good interobserver agreement. There was a statistically significant difference in mitotic counts between subtypes of follicular lymphoma as well as a gradient among subtypes, with the lowest mitotic activity in the poorly differentiated lymphocytic subtype and highest in the undifferentiated subtype. A multivariate statistical analysis of clinical and pathologic variables showed that mitotic figures were not of prognostic significance.

Humans↗

PubMed1987

Primary lymphomas of the liver. Report of six cases and review of the literature.

Six cases of diffuse large cell lymphoma (DLCL) of the liver were studied with immunohistochemistry for common leukocyte antigen (CLA), lysozyme, alpha-1-antitrypsin (AAT), and kappa and lambda light chains on paraffin-embedded tissues. All six cases were positive for CLA. Four of the six cases showed staining for lysozyme and AAT (three focal and one diffuse staining). In three cases, frozen tissue for monoclonal antibodies and glutaraldehyde-fixed tissue for electron microscopic examination were available. Two of these showed B-cell phenotypes with monoclonal antibody studies. Electron microscopic examination on these two B-cell lymphomas showed scant cytoplasm and a paucity of cytoplasmic organelles. The third case did not show definite B- or T-cell surface markers but did show strong Leu-M1 and OKM1 staining. Electron microscopic examination of the tumor cells showed a prominent Golgi apparatus, abundant cytoplasm with numerous cytoplasmic organelles and phagolysosomes. However, DNA hybridization studies on this tumor showed immunoglobulin heavy and kappa light chain gene rearrangements typical of a B-cell lymphoma. All six lymphomas were solitary liver masses without evidence of disease elsewhere. The mean age for the six patients was 56.2 years (four males, two females).

Aged↗

PubMed1987

Acute myelofibrosis. Immunohistochemical study of four cases and comparison with acute megakaryocytic leukemia.

Four cases of acute myelofibrosis are contrasted to three cases of acute megakaryocytic leukemia. The cases were clinically indistinguishable. Light microscopic examination of hematoxylin and eosin-stained bone marrow biopsy specimens from the cases of acute myelofibrosis showed a trilinear proliferation of mature and immature hematopoietic cells, increased numbers of mature magakaryocytes, and marked fibrosis. In contrast, the blast cells in the cases of acute megakaryocytic leukemia showed a continuous spectrum of differentiation from small blasts to megakaryoblasts. Immunoperoxidase staining showed the blast cells in all three cases of acute megakaryocytic leukemia to be strongly positive for Factor VIII, a marker of megakaryocytic differentiation. These same blasts did not stain with markers of myelomonocytic (lysozyme), lymphocytic (Hle), and myeloid (Leu-Ml) differentiation. In contrast, the blast cells in all four cases of acute myelofibrosis were Factor VIII, Hle, and Leu-Ml negative but did occasionally stain with anti-lysozyme.

Acute Disease↗

PubMed1987

Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma.

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.

Adult↗

PubMed1987

Treatment of poor prognosis non-Hodgkin's lymphoma using cyclophosphamide and total body irradiation regimens with autologous bone marrow rescue.

Twenty patients with poor prognosis non-Hodgkin's lymphoma received regimens which employed cyclophosphamide and total body irradiation followed by autologous bone marrow rescue. There were two toxic deaths. All 10 patients with residual disease prior to treatment achieved a complete remission. Ten patients survive disease free from 1.4 to 9.5 years and median survival exceeds 2.9 years. The actuarial 3-year disease-free survival is 50%. Treatment with cyclophosphamide and total body irradiation followed by autologous bone marrow infusion is an effective salvage regimen for poor prognosis lymphoma. Durable long-term remissions can be achieved.

Adolescent↗

PubMed1986

Richter's syndrome with two different B-cell clones.

The diagnoses of chronic lymphocytic leukemia (CLL) in prolymphocytic transformation, and diffuse large cell lymphoma (DLC), were made simultaneously in a 71-year-old man. The DLC showed mu lambda surface immunoglobulin. The CLL in a lymph node and in the peripheral blood showed mu kappa. Immunoglobulin gene DNA analysis confirmed the presence of different rearrangements in the heavy and light chain genes of the CLL and DLC. Other cases reported of Richter's syndrome are discussed, and it is concluded that there may be two types of Richter's syndrome, those arising from transformation of a single clone, and those occurring from expansion of two morphologically and immunologically distinct clones, as, it is believed, is the case in this patient.

Aged↗

PubMed1986

Merkel cell (small cell) carcinoma of the skin: immunohistochemical and ultrastructural demonstration of distinctive perinuclear cytokeratin aggregates and a possible association with B cell neoplasms.

Three cases of Merkel cell (small cell) carcinoma of the skin are presented with immunohistochemistry for epithelial and neuroendocrine antigens. All three cases showed distinctive punctate perinuclear cytoplasmic positivity for cytokeratin which corresponded to aggregates of intermediate filaments, seen ultrastructurally in two cases. Epithelial membrane antigen was also identified in two cases. Only one case showed cytoplasmic positivity for neuron specific enolase, and immunostaining for a battery of polypeptide hormones was negative. The demonstration of cytokeratin perinuclear inclusions provides a distinctive immunohistochemical feature to aid in their diagnosis. Two of the three patients had chronic lymphocytic leukaemia years before the diagnosis of Merkel cell carcinoma. The possible association of lymphoproliferative disorders, particularly B cell tumours, and Merkel cell carcinoma is discussed.

Aged↗

PubMed1986

Localized herpes simplex lymphadenitis.

Despite the marked immunocompromised status of most affected patients, visceral herpes simplex virus (HSV) infections in adults remain localized to the esophagus, with only rare examples of dissemination. Lymph node involvement with herpes simplex has been noted in three reported cases, but only in the context of a widespread fatal infection. This report describes two patients who presented with localized herpetic lymphadenitis documented by light microscopy, immunohistochemistry, and DNA hybridization technics.

Aged↗