Summary Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 ig kg-'day-'. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.
Summary Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to intravenous normal saline flush and they did not develop these complications. Significant decreases of the platelet count and total leucocyte, neutrophil and lymphocyte counts were seen in the first 24 h after treatment at the dose of 65 jig m2. Immediate decreases in haemoglobin of up to 1.9g dl-' were also noted in patients treated with 65 iLg m2, in the absence of clinical evidence of bleeding or haemodynamic compromise. No effect was observed on the incidence of haemopoietic progenitor cells in the marrow. Some patients' neutrophils demonstrated enhanced superoxide radical formation in response to in vitro stimulation with opsonised zymosan (a bacterial polysaccharide) but in the absence of this additional stimulus, no bryostatin 1 effect was observed. Lymphocyte natural killing activity was decreased 2 h after treatment with bryostatin 1, but the effect was not consistently seen 24 h or 7 days later. With the dose schedule examined no antitumour effects were observed. We recommend that bryostatin 1 is used at a dose of 35 to 50 jg m-2 two weekly in phase II studies in patients with malignancies including lymphoma, leukaemia, melanoma or hypernephroma, for which pre-clinical investigations suggest antitumour activity.
Intravitreal injections (IVI) of anti–vascular endothelial growth factor (anti–VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy. Effective therapy requires adherence to a schedule of iterative IVI as well as routine clinic appointments. The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in the reduction of attendance at scheduled clinic visits and IVI. In this study, we attempted to analyze the effect of COVID-19 on compliance with anti–VEGF therapy. A total of 636 eyes received injections during a 4-week period of the COVID-19 outbreak in the Retina Clinic. The number of clinic visits for IVI during 1 month from March 15 to April 14 of 2020 was compared to a similar time period in each of the last 4 years. The study demonstrates a decrease in clinic visits for IVI when compared with the same 4-week interval in the four previous years. Based on the trend of the previous 4 years, 10.2% of the year’s total was expected for this time period. Using this model, the 636 reported number of injections for the March–April 2020 period was ~ 5%. This represents a decrease of ~ 50% of the expected IVI for this time period. The COVID-19 outbreak in Israel severely impacted compliance with anti–VEGF treatments.
The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials.
We studied blood lymphocytes of human immunodeficiency virus (HIV)-seropositive and -negative homosexual men for the presence of T(8;14) translocations that recombine c-myc and immunoglobulin heavy-chain (IgH)p/ IgHa switch regions. Clones with T(8;14) translocations were detected in 10.5% (12/114) of the HIV-positive and in 2.0% of the 99 uninfected patients. The majority of recombinations were found at a single time point only. Four patients, however, harbored multiple (up to four) and persistent (up to 9 years) translocation-positive cell clones. No correlation between the presence of these aberrant lymphocytes and a later lymphoma could be established. The exon 1/intron 1 region of the recombined c-myc was investigated for the presence of point mutations and these were found in the nonpersistent clones. Additional alterations detected in these clones included duplications and a deletion in the c-myc gene. The pattern of base substitutions indicates that they were introduced after the translocation event.Individuals infected with the human immunodeficiency virus (HIV) develop non-Hodgkin lymphomas (NHLs) at a frequency 60 times higher than the general population (1). AIDS NHLs are usually derived from B cells and the majority of them carry rearrangements and point mutations in the oncogene c-myc (2-4). Several mechanisms by which lymphomagenesis in these immunocompromised patients may be promoted have been proposed (for review, see ref. 5): (i) the absence of immunosurveillance, (ii) abnormal growth factor expression, and (iii) chronic antigenic stimulation.NHL in AIDS patients, in contrast to NHL in the general population, originates in extranodal locations as frequently as at nodal sites (6, 7). Here we show that c-myc rearrangements can be detected in blood lymphocytes of some lymphomanegative individuals over extended periods of time.
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