PubMed Health⌕ Search

Biomedical subjects

G Pinkus

Publications and source records attributed to G Pinkus.

18 recordsLinked to original sources
PubMed1997

Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma.

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.

AIDS-Related Opportunistic Infections↗
PubMed1997

Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease.

PURPOSE: The patterns of presentation, histologic pattern (nodular or diffuse), treatment, and long-term outcome were studied in patients with lymphocyte-predominant (LP) Hodgkin's disease (HD) to determine whether these patients should be treated differently than patients with other subtypes of HD. PATIENTS AND METHODS: Pathology was reviewed for 97 patients with an initial diagnosis of LPHD made between 1970 and 1993. Seventy-five patients had LPHD on review: 55 had nodular LPHD, 14 had diffuse LPHD, and six had LP histology without subclassification. There were 60 males (80%) and 15 females (20%). Sixty-six patients (88%), presented with clinical stage (CS) I or II disease. Seventy-one patients were treated at the Joint Center for Radiation Therapy (JCRT) and were considered for analysis of treatment outcome. Sixty-one of these 71 were treated with radiation (RT) alone; 17 received mantle RT alone, 27 mantle and paraaortic RT, and seven total-nodal irradiation (TNI). Ten patients with subdiaphragmatic HD received pelvic and paraaortic RT. Of the 10 remaining patients, four were treated with RT and chemotherapy (CT) and six were treated with CT alone. The median follow-up time was 10.8 years. RESULTS: The 10-year actuarial freedom-from-first-relapse (FFR) and 10-year overall survival rates for the 71 patients with LPHD treated at the JCRT were 80% and 93%, respectively. The 10-year actuarial FFR by nodular (n = 51), diffuse (n = 14), and unspecified (n = 6) histologic pattern was 74%, 100%, and 60%, respectively. Overall, 14 of 71 patients have relapsed: nine of 61 with stage IA, IB, or IIA disease and five of 10 with stage IIB to IVB disease have relapsed. The median time to relapse was 53 months. Nine of 71 patients have died. Only one death has been from HD: five patients died of second cancers, two of cardiac disease, and one of alcoholic liver cirrhosis. Of seven patients with second malignancies, five died. None of the second malignancies were non-Hodgkin's lymphoma (NHL). CONCLUSION: Patients with LPHD have different patterns of presentation, sex and age distribution, and likelihood of occult abdominal disease than patients with nodular-sclerosing (NS) or mixed-cellularity (MC) disease. The median time to relapse for LP patients was later than reported for other histologic subtypes; however, there was no pattern of continuous late relapse. With pathologic staging and standard treatment, mortality from LPHD is low; nearly all deaths have been cardiac- or second tumor-related. This suggests that less aggressive treatment for LPHD might continue to yield excellent results, while perhaps lowering the long-term risk of complications.

Adolescent↗
PubMed1994

Histopathologic grading of nodular sclerosis Hodgkin's disease. Lack of prognostic significance in 254 surgically staged patients.

BACKGROUND: The cellular composition of nodular sclerosis Hodgkin's disease (NS-HD) varies greatly from patient to patient. It is unclear whether subclassifying NS-HD based on cellular composition has prognostic value, because reported studies examining this issue have shown conflicting results. METHODS: The initial pathology slides of 254 surgically staged patients with NS-HD treated at the Joint Center for Radiation Therapy were reviewed and subclassified according to British National Lymphoma Investigation criteria. The median follow-up time was 123 months. RESULTS: A total of 211 patients were classified NS I histology (83%), and 43 patients were classified NS II (17%). There were no differences in the distribution of NS I/NS II patients by age, number of sites of disease, B symptoms, or extent of mediastinal disease. Patients with NS II disease were more likely to be male (P = 0.001), and to have pathologic Stage I-II disease (P = 0.07). The 15-year actuarial rates of disease-free survival were 77 and 80% for NS I and NS II patients, respectively (P = not significant). The 15-year overall survival rates were 87 and 93% for NS I and NS II, respectively (P = not significant). No differences were seen between NS I and NS II patients for overall or disease free survival when analyzed separately by pathologic stage or by initial treatment. Similarly, no differences between NS I and NS II patients were seen in the large subgroup of 155 pathologic stage IA-IIA patients treated with radiation therapy alone. When other histologic parameters were analyzed separately, no differences were seen in the frequency of relapse between the groups based on extent of necrosis, atypia, fibrosis, variant atypia, variant syncytia, eosinophilia, or number of mitoses. CONCLUSIONS: The histologic subclassification of Hodgkin's disease had no prognostic significance in this group of surgically staged, uniformly treated patients.

Adolescent↗
PubMed1993

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia.

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.

Adult↗
PubMed1993

Primary Ki-1 anaplastic large-cell lymphoma in adults: clinical characteristics and therapeutic outcome.

PURPOSE: A study was undertaken to improve our understanding of the clinicopathologic features and therapeutic outcome for adults with primary Ki-1 anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: A retrospective review of records of 31 adult patients with primary Ki-1 ALCL was performed. The analysis included stage and distribution of disease, tumor-cell phenotype, response to initial and salvage therapy, and disease-free and overall survival. RESULTS: The median age of patients was 44 years (range, 16 to 86). Forty-eight percent of patients tested had lymphomas of T-cell phenotype, 30% lymphomas of B-cell phenotype, and 22% of non-T-, non-B-cell phenotype. Twenty-nine percent of patients had stages I and II disease, 65% demonstrated extranodal involvement, and 32% had skin involvement at presentation. Most patients received intensive chemotherapy and 48% achieved a sustained complete remission (CR), with an additional 17% of patients treated successfully with salvage therapy. Stage was highly predictive of achieving a sustained CR, but bulk disease and B symptoms did not predict for relapse after initial therapy or survival. Of seven patients who underwent autologous bone marrow transplantation (ABMT), three remain disease-free 9 to 42 months after transplant. CONCLUSION: Patients with Ki-1 ALCL have a high frequency of advanced-stage disease and extranodal involvement and are more likely to have tumors of T-cell phenotype than patients with large-cell lymphoma. However, response to standard lymphoma chemotherapy is similar to other patients with large-cell lymphoma, with a high remission rate in early-stage disease. Patients with advanced-stage disease have a poor remission duration and may require more intensive therapy, as may also be the case with large-cell lymphoma.

Adolescent↗
PubMed1993

Large-cell and immunoblastic lymphoma of the mediastinum: prognostic features and treatment outcome in 57 patients.

PURPOSE: A retrospective study was performed to define clinical characteristics and therapeutic outcome for patients with large-cell and immunoblastic lymphoma of the mediastinum. PATIENTS AND METHODS: Fifty-seven patients who presented with primary, mediastinal large-cell and immunoblastic lymphoma were retrospectively studied to determine initial sites of disease, radiologic characteristics, treatment, outcome, and factors that have prognostic significance for progression-free and overall survival. RESULTS: Fifty-six of the 57 patients had disease that was confined to sites above the diaphragm. Bulky disease and extensive intrathoracic infiltration were common in these patients. All patients were treated with intensive chemotherapy regimens, and 44% of patients received chest irradiation. The overall 5-year survival by Kaplan-Meier estimation was 50% with a freedom-from-relapse rate of 45%. Predictors of disease relapse after chemotherapy included the presence of a pleural effusion (P = .015), a number of involved extranodal sites (P < .01), and a lactic dehydrogenase (LDH) ratio > 3.0 (LDH value/upper limit of assay; P = .04) as well as an incomplete treatment response as evidenced by residual mass on chest radiograph (P = .02) or persistent gallium 67 avidity (P = .01) after chemotherapy. Predictors of decreased survival included the presence of pleural effusion (P = .001), the number of involved extranodal sites (P = .022), and a positive posttreatment 67Ga scan (P = .027). CONCLUSION: Patients with primary mediastinal large-cell and immunoblastic lymphoma have an approximate 50% chance of surviving disease-free after initial therapy. The presence of pleural effusion at presentation was associated with an extremely poor outcome. Bulk disease per se was a negative predictive factor only in patients without pleural effusions when compared with patients who did not have bulk disease. In addition, all patients with involvement of two or more extranodal sites relapsed when treated with standard chemotherapy.

Actuarial Analysis↗
PubMed1990

Treatment of low-grade and intermediate-grade lymphoma with intensive combination chemotherapy results in long-term, disease-free survival.

To define the role of intensive combination chemotherapy in the treatment of low-grade or intermediate-grade lymphomas, the authors report results in 49 patients treated with intermediate-dose or high-dose methotrexate, bleomycin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cytoxan (cyclophosphamide), vincristine, and dexamethasone (m/M-BACOD) with long-term follow-up. The complete response rate was 59% (29 of 49), including 67% (eight of 12) with low-grade and 57% (21 of 37) with intermediate-grade disease. The median survival for the entire group was 81 months. The 29 complete responders had a long median survival of 131 months. Forty-five percent (13 of 29) of the complete responders, 27% of the entire group, continue in remission with a median disease-free survival of 76 months. This includes five of 19 patients with diffuse poorly differentiated lymphoma, a disease generally characterized by early relapse. Twelve patients achieved a partial response and had a shorter median survival of 53 months, whereas nonresponders survived a median of less than 5 months. Late relapse was noted in patients with low-grade and intermediate-grade disease. Age (younger than or older than 60 years) was the only predictor of long-term survival. These data indicate very long disease-free survival can be achieved in low-grade and intermediate-grade lymphomas after attaining a complete remission. Intensive doxorubicin containing chemotherapy can be considered as an option for patients with advanced low-grade lymphoma but can only be proven to be superior to single-agent chemotherapy or no initial therapy by controlled randomized trails.

Adult↗
PubMed1990

Prognostic factors for positive surgical staging in patients with Hodgkin's disease.

Staging laparotomy was performed as part of the routine recommended diagnostic evaluation following clinical staging (CS) in 692 patients presenting with supradiaphragmatic Hodgkin's disease (HD). Various clinical factors were analyzed by multivariate analysis for prediction of abdominal involvement. Factors that were statistically significant for predicting disease below the diaphragm included CS III-IV disease (P less than .001), B symptoms (P less than .001), mixed cellularity (MC) or lymphocytic depletion (LD) histology (P = .017), number of supradiaphragmatic sites greater than or equal to 2 (P = .001), male sex (P = 0.034) and age greater than or equal to 40 years (P = .004). Separate analyses were performed for various subgroups of CS IA-IIA, CS IB-IIB, CS IIIA-IVA, and CS IIIB-IVB patients. Upstaging was seen in 0% to 55% of CS I-II patients based on subgroup. Male sex, B symptoms, and number of sites above the diaphragm greater than or equal to 2 all independently predicted for positive surgical staging in CS I-II patients. Sixty-four percent of CS I-II patients who were upstaged had extensive abdominal disease by positive lower abdominal nodes or multiple splenic nodules (greater than or equal to 5). Downstaging (to pathological stage [PS] I-II) was seen in 9% to 68% of patients with CS III-IV disease based on subgrouping. Age greater than or equal to 40, MC or LD histology, and B symptoms all independently predicted for positive surgical staging in CS III-IV patients. Downstaging was more frequently seen in CS IIIA-IVA patients (55%) than in patients who were CS III-IVB (22%). Four subgroups of patients who had a low probability (less than 10%) of stage or treatment change following laparotomy were identified. These included CS IA female patients, CS IA male patients with lymphocyte predominance histology or high neck presentations, and patients with CS IIIB-IVB disease and account for 21% of the study population. Staging laparotomy altered the stage and treatment of a significant number of the remaining 79% patients and should continue to be recommended for this group of patients.

Abdominal Neoplasms↗
PubMed1989

Cell proliferation in non-Hodgkin's lymphomas. Digital image analysis of Ki-67 antibody staining.

Ki-67 is a monoclonal antibody to a nuclear antigen present in cycling human cells but not in resting cells. The authors have performed immunoperoxidase on non-Hodgkin's lymphomas using Ki-67 antibody in order to correlate proliferation rates with tumor grade and type, and compare Ki-67 staining with S-phase content as determined by flow cytometry. Ki-67 staining of 109 sections was quantitated using a digital image analysis system (CAS 100). There was a significant difference among mean overall Ki-67 staining values in Working Formulation low (13.7%), intermediate (42.6%), and high grade tumors (57.9%, P less than 0.00001). The level of significance improved when a revised grading system was formulated based on proliferative activity, with the inclusion of diffuse large cell lymphomas in the high grade category. Within nodular and a few diffuse lymphomas, there were well-defined proliferation centers in which Ki-67 staining showed no correlation with grade. Flow cytometric DNA determination was performed on 74 specimens, and there was a positive correlation between Ki-67 positivity and S phase content (r = 0.66). It is concluded that Ki-67 staining of tissue sections is an alternative to flow cytometric quantitation of cell cycle activity in lymphomas, and provides the advantage of revealing histologic patterns of proliferation. By including G1 phase cells, Ki-67 staining allows a more complete determination of total cell cycle activity in lymphomas.

Antibodies, Monoclonal↗
PubMed1985

Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation.

A case of perianal and perineal extramammary Paget's disease in a male is reported. The presence of gross cystic disease fluid protein--a new marker of apocrine epithelia--in Paget's cells provides additional insight into the histopathogenesis of this condition. This marker may be a valuable diagnostic adjunct in evaluating intra-epithelial malignancies at a variety of anatomic sites.

Aged↗
PubMed1983

Clinical, pathologic and immunologic features of patients with non-Hodgkin's lymphoma in a leukemic phase. A retrospective analysis of 34 patients.

A retrospective review of 34 patients with non-Hodgkin's lymphoma and a leukemic phase was undertaken. The median survival after onset of a leukemic phase was 30 months for patients with nodular poorly differentiated lymphocytic lymphoma which was significantly longer than 19 months for diffuse poorly differentiated lymphocytic lymphoma, and 2 months for diffuse histiocytic and undifferentiated lymphoma. Clinical features of patients with diffuse histologies that contributed to a poor prognosis included advanced stage of disease as well as age. Underlying lymph node histology also defined features of the leukemic phase which included duration, peak leukocyte count, and in some instances, distinctive morphologic characteristics of circulating malignant cells. Although small sample size did not permit definitive correlations of immunological subtype and survival, heterogeneity was noted, suggesting that clearer stratification of these patients with immunologic techniques may be useful in assessing prognosis in future investigations.

Adult↗
PubMed1976

Chemoprophylaxis in inactive tuberculosis: long-term evaluation of a Canadian trial.

A trial of chemoprophylaxis to prevent reactivation of tuberculosis in persons with inactive disease who had never had adequate chemotherapy was conducted in Canada in the mid-1960s. Preventive drug treatment consisted of either isoniazid (INH) alone or INH plus para-aminosalicylic acid (PAS), for a maximum of 18 months. Long-term evaluation in 1974 of 1571 treated patients and 834 control patients demonstrated clearly the substantial and sustained value of adequate chemoprophylaxis in reducing the risk of reactivation. Among those who took INH alone for 6 months or more the annual reactivation rate was 1.2 per 1000 persons, while among those who took INH plus PAS the rate was 0.38/1000. These rates were, respectively, 70 and 90% less than the average rate in the controls, 3.9/1000. Among those who underwent chemoprophylaxis for less than 6 months the annual reactivation rate was 3.7/1000, similar to that in the controls. Cost-benefit analysis showed chemoprophylaxis to be economically sound. Despite the recent increasing application of this preventive measure, there are still many persons living in Canada who could benefit substantially from a course of chemoprophylaxis.

Aminosalicylic Acids↗
PubMed1976

Unusual noninfectious granulomas of the lung.

Illustrative cases of pulmonary granulomas with angitis and plasma cell granuloma of the lungs are presented. Experimental evidence suggests that the common pathogenesis of these processes is a cell-mediated immune response. Radiographic findings of these entities--nodules or infiltrates, some with cavities--are non-specific. Effective treatment is available for some of these processes. Lung biopsy as early as possible is recommended.

Adult↗
PubMed1969

In Canada: a trial of chemoprophylaxis in inactive tuberculosis.

One thousand five hundred and thirty-six patients with inactive tuberculosis were given a course of preventive treatment consisting of either INH alone or INH and PAS while 840 similar patients served as a control group. Discontinuation of the treatment was frequent and was usually caused by development of complaints which the patients ascribed to the drugs they were taking.The annual reactivation rate among controls was 4.9 per 1000. During the period of taking drugs the treated group suffered a reactivation rate of 0.7 per 1000 and those who had taken the medication for at least six months suffered a subsequent annual reactivation rate of 1.3 per 1000. The rate for those who discontinued treatment in the first six months was 5.1 per 1000. There were no reactivations in patients who took INH and PAS for over six months. Bacilli from two of the patients with reactivations who were treated for a prolonged period with INH alone showed resistance to this drug.Chemoprophylaxis of inactive cases is a potent weapon in tuberculosis control; however, it requires thorough motivation and supervision.

Aminosalicylic Acids↗