PubMed HealthSearch

Biomedical subjects

S Riddell

Publications and source records attributed to S Riddell.

7 recordsLinked to original sources

High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia.

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.

Acute Disease

Requirements for T cell recognition and elimination of retrovirally-transformed cells.

An adoptive therapy model has been utilized to examine the requirements for T cells to promote eradication of a disseminated, retrovirus-induced, syngeneic leukemia. Complete tumor elimination required that the transferred T cells proliferate in the host and mediate an anti-tumor effect for more than 30 days. Non-cytolytic L3T4+ T helper (Th) cells were capable of eliminating disseminated tumor without the participation of Lyt-2+ cytotoxic T cells (Tc). Purified or cloned Lyt-2+ T cells were also effective in therapy, but required the concurrent administration of either L3T4+ Th or interleukin 2 (IL-2) for optimal efficacy. L3T4+ Th appear to function via secretion of lymphokines that activate macrophages to a cytotoxic state. Lyt-2+ Tc, in addition to direct cytotoxicity, may mediate tumor eradication in part by secretion of lymphokines that activate in vivo tumoricidal macrophages. These studies suggested that the reported efficacy of individual T cell subsets in therapy of particular tumors might not reflect resistance or susceptibility to a cytotoxic effector mechanism, but rather the efficiency with which a T cell subset is activated by the tumor and/or recognizes the tumor antigen. Methods were developed to independently assess the activation and proliferation requirements of each subset. L3T4+ Th required that macrophages degrade tumor antigens in lysosomes and present the antigens in the context of class II molecules, and produced IL-2 and IL-4 as endogenous growth factors. By contrast, Lyt-2+ T cells recognized the tumor directly, required macrophages only to produce IL-1 for activation, and produced IL-2 but not IL-4 as an endogenous growth factor. The ability of T cell subsets to recognize the distinct retroviral tumor antigens expressed on FBL leukemia was assessed using cell lines or recombinant vaccinia viruses transfected with selected retroviral genes. Highly selective antigen recognition was detected, with Lyt-2+ Tc cells recognizing products of gag but not envelope genes, and L3T4+ Th recognizing envelope but not gag products. The results suggest that even complex unique tumor antigens may elicit only limited host T cell responses.

Animals

Colonization with slime-positive coagulase-negative staphylococci as a risk factor for invasive coagulase-negative staphylococci infections in neonates.

Mucocutaneous cultures obtained at admission and subsequent weekly nasopharyngeal cultures were obtained on 182 infants in the neonatal intensive care unit (NICU) over 3 months to assess whether a relationship existed between colonization with coagulase-negative staphylococci and invasive infection, particularly with respect to slime production. Nasopharyngeal colonization by coagulase-negative staphylococci occurred in a mean of 58% of infants weekly, with an equal prevalence of slime-positive and slime-negative isolates over time. Colonization of the nasopharynx on admission increased from 8.9% of those admitted within the first day of life to 33% of those admitted thereafter (p less than 0.005). The presence of slime-positive coagulase-negative staphylococci on admission was not predictive of later patterns of colonization with respect to slime. Of infants not colonized on admission who had subsequent cultures, 72% became colonized with coagulase-negative staphylococci that were equally likely to be slime-positive or slime-negative. The incidence of invasive infections was 4.4%. Infants with slime-positive mucocutaneous colonization were more likely to develop invasive coagulase-negative staphylococci disease than infants with slime-negative or no colonization (8.4% versus 1.1%; p less than 0.025). The incidence of slime-positive coagulase-negative staphylococci isolates from blood cultures was 6/7 (86%) whereas those from mucocutaneous cultures was 131/260 (50%) (p = 0.06). Colonization with slime-positive coagulase-negative staphylococci is a significant risk factor for developing invasive coagulase-negative staphylococci disease and these organisms are responsible for the majority of coagulase-negative staphylococci invasive infections.

Coagulase

The double gammopathies. Clinical and immunological studies.

A retrospective review of 1135 patients with paraproteinemias recorded 28 (2.5%) as having two M components. This group included 11 patients with myeloma, 6 with lymphoproliferative disease, 5 with a nonlymphoproliferative malignancy, and 6 with a double gammopathy of undetermined significance. In 13 cases in which the M components were measured over a period of time, three distinct patterns were observed, which may reflect the cellular and subcellular origin of the two proteins: 1) In 2 cases the minor component remained relatively stable while the dominant protein changed with time and treatment, suggesting the origin to be two cell lines--the minor arising from a quiescent clone of the monoclonal gammopathy of undetermined significance, and the major M component arising from a more rapidly proliferating plasma cell line; 2) a discordant pattern was seen in 4 patients, suggesting that the two M components arose from two separate plasma cell clones; 3) seven cases in which the proteins behaved in a concordant manner probably arose from a single plasma cell clone with incomplete class switching, producing two M components with different heavy chains.

Aged