Search PubMed⌕ Search

Biomedical subjects

R Ambinder

Publications and source records attributed to R Ambinder.

12 recordsLinked to original sources
PubMed2002

Gemcitabine as first-line therapy in patients with metastatic breast cancer: a phase II trial.

OBJECTIVES: This phase II study was conducted to evaluate the efficacy and safety of gemcitabine in patients with metastatic breast cancer (MBC). METHODS: Women with histologically or cytologically confirmed bidimensionally measurable MBC not amendable to curative surgery or radiation were eligible. Prior chemotherapy for metastatic disease was not permitted. Patients received gemcitabine 1,200 mg/m(2) on days 1, 8 and 15 for 3 weeks every 28 days for a maximum of 8 cycles. RESULTS: Thirty-nine patients, with a median age of 58 years, were enrolled. The overall response rate for the 35 evaluable patients was 37.1% (95% confidence interval [CI], 21.5-55.1%), with 2 complete responses and 11 partial responses. Median time to progression and survival were 5.1 months (95% CI, 3.5-8.8 months) and 21.1 months (95% CI, 11.0-26.9 months), respectively. Chemotherapy was well tolerated, with a median of 4 cycles completed. Grade 4 toxicities were 1 infection and 1 abnormal pulmonary function. Grade 3 neutropenia and thrombocytopenia occurred in 30.3% and 6.3% of patients, respectively. The most common grade 3 non-hematologic toxicity was nausea/vomiting (10.3%). Five of 21 patients had improved Karnofsky performance status (KPS) scores. CONCLUSION: Single-agent gemcitabine is active and well tolerated as first-line treatment in patients with MBC.

Adolescent↗
PubMed2001

Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.

PURPOSE: This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART. PATIENTS AND METHODS: Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir. RESULTS: The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL. CONCLUSION: Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.

Adult↗
PubMed1999

PCR detection of adenovirus in a bone marrow transplant recipient: hemorrhagic cystitis as a presenting manifestation of disseminated disease.

Adenoviruses (AdV), causing fatal disseminated infections in bone marrow transplant (BMT) recipients, are associated not only with hemorrhagic cystitis (HC) but also with hepatitis, conjunctivitis, and viral interstitial pneumonia. The importance of this virus as a cause of disseminated disease, however, has remained underappreciated. AdV infection has been diagnosed primarily through the use of cell culture. The fact that cell culture is insensitive for detecting this virus has hindered recognition of the role that AdV may play in morbidity and mortality in BMT recipients. To emphasize these points, we describe a patient who presented with HC due to AdV serotype 11, genotype c, and died with disseminated infection. In addition to cell culture, this study used a newly developed PCR-based method, capable of detecting all AdV serotypes tested, including different genotypes of serotype 11. The PCR result was positive in all culture-positive samples, including samples of urine, conjunctiva, and bronchoalveolar lavage (BAL). Importantly, the PCR method provided evidence of urinary shedding of AdV in a pretransplant, culture-negative specimen and showed dissemination in a subset of culture-negative specimens, including BAL, blood, and bone marrow samples. The lack of widespread awareness of the fact that localized infections may presage dissemination, and the previous associated lack of rapid, sensitive diagnostic assays, has impaired recognition of AdV infections in patients undergoing BMT. Early detection may contribute to therapy modification and avoidance of unwarranted diagnostic procedures. It may also assist in epidemiologic control of this highly infectious pathogen and lead to a renewed interest in preventive and therapeutic approaches.

Adenovirus Infections, Human↗
PubMed1999

Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end.

Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV8) DNA is found consistently in nearly all classical, endemic, transplant, and AIDS-associated KS lesions, as well as in several AIDS-associated lymphomas. We have previously sequenced the genes for the highly variable open reading frame K1 (ORF-K1) protein from more than 60 different HHV8 samples and demonstrated that they display up to 30% amino acid variability and cluster into four very distinct evolutionary subgroups (the A, B, C, and D subtypes) that correlate with the major migrationary diasporas of modern humans. Here we have extended this type of analysis to six other loci across the HHV8 genome to further evaluate overall genotype patterns and the potential for chimeric genomes. Comparison of the relatively conserved ORF26, T0.7/K12, and ORF75 gene regions at map positions 0. 35, 0.85, and 0.96 revealed typical ORF-K1-linked subtype patterns, except that between 20 and 30% of the genomes analyzed proved to be either intertypic or intratypic mosaics. In addition, a 2,500-bp region found at the extreme right-hand side of the unique segment in 45 HHV8 genomes proved to be highly diverged from the 3,500-bp sequence found at this position in the other 18 HHV8 genomes examined. Furthermore, these previously uncharacterized "orphan" region sequences proved to encompass multiexon latent-state mRNAs encoding two highly diverged alleles of the novel ORF-K15 protein. The predominant (P) and minor (M) forms of HHV8 ORF-K15 are structurally related integral membrane proteins that have only 33% overall amino acid identity to one another but retain conserved likely tyrosine kinase signaling motifs and may be distant evolutionary relatives of the LMP2 latency protein of Epstein-Barr virus. The M allele of ORF-K15 is also physically linked to a distinctive M subtype of the adjacent ORF75 gene locus, and in some cases, this linkage extends as far back as the T0.7 locus also. Overall, the results suggest that an original recombination event with a related primate virus from an unknown source introduced exogenous right-hand side ORF-K15(M) sequences into an ancient M form of HHV8, followed by eventual acquisition into the subtype C lineage of the modern P-form of the HHV8 genome and subsequent additional, more recent transfers by homologous recombination events into several subtype A and B lineages as well.

Alleles↗
PubMed1998

Feasibility of cellular adoptive immunotherapy for Epstein-Barr virus-associated lymphomas using haploidentical donors.

Epstein-Barr virus (EBV)-associated lymphomas following bone marrow or solid organ transplantation are often sensitive to immunomodulatory therapies. These have included withdrawal or reduction in immunosuppressive therapy in the solid organ transplant setting and adoptive cellular therapies in the bone marrow transplant (BMT) setting. We describe a strategy for generating EBV-specific cytotoxic T cell therapy lines with substantial killing activity against haploidentical targets. Weekly stimulation of peripheral blood mononuclear cells (PBMCs) for 3 weeks with the irradiated cells of an autologous EBV-transformed B lymphoblastoid cell line (B-LCL), followed by stimulation in the presence of IL-2, yielded T cell lines that were cytolytic for haploidentical B-LCLs but did not lyse haploidentical targets not expressing EBV antigens.

Adoptive Transfer↗
PubMed1995

Epstein-Barr virus and bone marrow transplantation.

The development of Epstein-Barr virus-associated posttransplantation lymphoproliferative disease correlates with increased viral burden in lymphocytes. Patterns of viral gene expression in tumors are complex and heterogenous. Conventional chemotherapy for postransplantation lymphoproliferative disease is sometimes associated with long-term disease-free survival. A promising new approach involves adoptive cellular immunotherapy with donor lymphocytes or T-cell lines. Allogeneic bone marrow transplantation has been successful in patients with an inherited lack of immune response to Epstein-Barr virus.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

BMT for severe aplastic anemia using cyclosporine.

Between 1984 and 1991 24 patients with severe aplastic anemia (SAA) were transplanted with HLA identical sibling donor BM. The overall long-term survival was 79 +/- 8%. The average age was 21 years (range 4-53 years) and the median pre-transplant disease duration was 35 days (range 12-2998 days). Over one-half (15 of 24) of the patients had received > 10 units of blood product transfusions prior to BMT. The pre-transplant conditioning regimen consisted of 200 mg/kg cyclophosphamide (CY). Cyclosporine (CYA) was administered from 2 days prior to BMT and continued for 6-12 months. Two of the 24 patients failed to achieve primary engraftment (FTE). One of these patients had autologous recovery of BM function and is alive and well. Five of the 22 patients who engrafted failed to sustain engraftment (FTSE). Of these, three are alive and well following a second BMT or marrow boost. Only 1 of the 22 patients who engrafted had clinically significant (i.e. Stage II-IV) acute GVHD. No patient developed chronic GVHD. Our results indicate that BMT following a regimen consisting of CY with the continuous use of CYA in the post-transplant period is well tolerated and associated with excellent long-term survival. The high incidence of secondary graft instability (i.e. FTSE), however, suggests that future studies should focus on post-transplantation immunomodulation.

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↗
PubMed1989

A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease.

A total of 151 unselected malignant and nonmalignant lymphoid tissue samples were surveyed by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Eight of 28 Hodgkin's disease (HD) samples (29%) had detectable EBV DNA. Both nodular sclerosis and mixed cellularity histologic results were positive. The tumor type with the next highest frequency, 8%, was diffuse large cell lymphoma. The presence of EBV DNA in some HD biopsies suggests that EBV may be a factor in the pathogenesis of this disease. Alternatively, its presence may be secondary to the immune deficiency characteristic of HD. The clonal B-lymphocyte expansions reported in some cases of HD may result from EBV infection.

Blotting, Southern↗
PubMed1984

Structural organization of human herpesvirus DNA molecules.

The herpesviruses are among the largest and most complex of all DNA viruses, and their genomes display an astonishing diversity in size, structure, and organization. In 1974, the features of large inverted repeats and structural isomerization were first discovered, and these proved to be characteristic properties of many herpesvirus genomes. Since then, research using the powerful techniques of modern molecular biology has revealed a great deal of comparative structural information about the arrangement of repetitive sequences and the location, structure, and primary nucleotide sequences of the genes for several easily assayed or abundantly expressed gene products. Extensive restriction enzyme cleavage maps and complete sets of cloned DNA fragments have been constructed for each of the five human herpesviruses, HSV-1, HSV-2, CMV, EBV, and VZV, and the entire 175,000-bp nucleotide sequence of EBV DNA has been determined. Based on these maps and reagents, the procedures of "DNA fingerprinting" and "dot hybridization" are proving useful at a clinical level for characterization of isolates and studying herpesvirus epidemiology. Strain differences, localized heterogeneity, tandem-repeat-defective genomes, and sites of cell-virus DNA homology have been described in some detail. The attention of basic researchers is now turning to equating structure with function, and rapid progress is expected in studies aimed at a better understanding of the mechanisms of viral DNA replication, maintenance of the latent state, reactivation, transformation, packaging, and regulation of the lytic cycle, etc using cloned functionally active DNA fragments, isolated intact genes and promoters, and DNA transfection and in vitro expression systems.

Base Sequence↗
PubMed1984

Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial.

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Adult↗