The interleukin-2 receptor: a target for immunotherapy.
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Biomedical subjects
Publications and source records attributed to C Goldman.
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Group A streptococci account for less than 1% of all surgical wound infections but are an important cause of nosocomial outbreaks. We report here a cluster of four group A streptococcal infections that occurred within an 11-day period on a single surgical service. The index case presented with toxic shock-like syndrome. Epidemiologic investigation did not identify any relationship between infections. Restriction endonuclease analysis and M and T typing found the four isolates to be unrelated. Restriction endonuclease analysis is a useful tool for determining relatedness of nosocomial isolates of group A streptococci.
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The BACTEC PLUS 26 (NR26) (Becton Dickinson, Towson, Md.) high-volume blood culture bottle replaced the less expensive smaller-volume NR6A bottle in our hospital. An audit carried out several months after their introduction revealed that only 17.5% of the NR26 bottles received the required blood volume. Several audits and educational programs were required in order to achieve a compliance rate of > 60%.
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This paper describes patient-therapist codocumentation, a method of creating and using jointly authored treatment-progress notes. Codocumentation has five basic elements: (1) Patient and therapist agree to share responsibility for documentation of treatment. (2) During the last several minutes of each session, the patient records, by dictation, his or her views about the important issues covered, while the therapist listens. (3) The therapist can then dictate his or her comments, in the presence of the patient. (4) The notes are transcribed from tape-recorded to written form between sessions. (5) The typed transcriptions are available for joint review by patient and therapist during subsequent sessions. Sharing responsibility for documentation of treatment using this method promotes bidirectional feedback between patient and therapist. Several examples illustrate how jointly authored progress notes can help in the management of countertransference, as well as transference components of common problems in psychotherapy. The implications of patient-therapist codocumentation for psychotherapy research, training and supervision, and risk management are potentially significant. Further experience is necessary to refine the indications for, and limitations of, patient-therapist codocumentation.
A randomized trial was conducted to assess the effect of leaving heparin locks in place longer than 72 hours. Three hundred and one patients were randomly assigned to one of two groups. Group A had the lock changed every 72 hours and Group B had the lock left in place up to 168 hours. Due to withdrawals following randomization, Group A contained 116 subjects and Group B 140 subjects. No significant differences were found between the two groups in relation to age, sex, medical condition, drug used, entries into the lock, minor complications, or incidence of phlebitis. The findings suggest that consideration could be given to extending insertion time up to 96 hours and possibly up to 118 hours.
We have proposed a multichain model for the high-affinity interleukin-2 (IL-2) receptor involving two IL-2-binding peptides, a 70/75 kilodalton (kD) and a 55 kD, reactive with the anti-Tac monoclonal antibody, which are associated in a receptor complex. With the use of coprecipitation analysis, radiolabeled interleukin-2 cross-linking procedures, and flow cytometric resonance energy transfer measurements, a series of additional peptides of molecular weight 22,000, 35,000, 40,000, 75,000 (non-IL-2 binding), 95,000-105,000, and 180,000 has been associated with the two interleukin-2-binding peptides. In contrast to resting T cells, the abnormal T cells of patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia, patients with select autoimmune disorders, and individuals rejecting allografts express the Tac peptide (p55) of the IL-2 receptor. To exploit this difference in Tac antigen expression, we have initiated therapeutic trials using unmodified anti-Tac, conjugates of anti-Tac with truncated Pseudomonas exotoxin PE-40, interleukin-2-truncated toxin fusion proteins, and alpha- and beta-emitting isotopic chelates of anti-Tac. Furthermore, by genetic engineering humanized hyperchimeric anti-Tac molecules have been prepared in which the molecule is entirely human IgG1, except for the small complementarity-determining regions that are retained from the mouse antibody. This "humanized" antibody manifested the ability to perform antibody-dependent cellular cytotoxicity absent in the original mouse monoclonal. The clinical application of anti-interleukin-2 receptor-directed therapy represents a new perspective for the treatment of certain neoplastic diseases and autoimmune disorders and for the prevention of allograft rejection.
Although Serratia marcescens is a well-known nosocomial pathogen, investigation of its hospital ecology has been limited by the lack of available typing techniques. During an investigation of the occurrence of this organism in a neonatal intensive care unit, we evaluated a number of such techniques. Using a selective medium, we conducted prospective surveillance of neonatal rectal colonization and environmental contamination with S. marcescens. In 8 months of surveillance, 5.1% (20 of 394) of the infants admitted to the unit became colonized. Most sink surfaces and drains were also culture positive. Differences between isolates could not be detected in biotypes from a commercial identification system (MicroScan) or by antibiograms, total protein fingerprints, or plasmid profiles. Serogrouping and genomic DNA restriction endonuclease analysis revealed the presence of six strains that colonized infants and a similar number of environmental strains. These two methods were concordant, with the exception that genomic DNA analysis demonstrated lack of relatedness between some strains within the same serogroup. DNA restriction endonuclease analysis was practical and reliable. The differences this method detected between environmental and neonatal strains provided strong evidence that the environment was not an important reservoir for S. marcescens in our neonatal intensive care unit.
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Between November 1 and 22, 1985, an outbreak of acute, nonbacterial gastroenteritis occurred in a 600-bed hospital in Toronto, Ontario, Canada. Illness in 635 of 2,379 (27%) staff was characterized by fatigue, nausea, diarrhea, and vomiting and had a median duration of 24-48 hours. The finding of virus-like particles measuring 25-30 nm in six stool specimens and low rates of seroresponse to Norwalk virus (3/39) and Snow Mountain agent (1/6) suggest that a Norwalk-like virus was responsible for the outbreak. The outbreak was of abrupt onset and high incidence, affecting 79 people in a single day. No common food or water exposure could be identified. The attack rate was greatest (69%) for staff who had worked in the Emergency Room. Of 100 patients and their companions who visited the Emergency Room on November 11-12 for unrelated problems, 33 (33%) developed gastroenteritis 24-48 hours after their visit, versus 0 of 18 who visited the Emergency Room on November 8 (p less than 0.001). An analysis of housekeepers who worked at least once during the period from November 9-13, which included those who became ill during the period of November 9-14, showed that the risk of becoming ill was four times greater for those who visited or walked through the Emergency Room than for those who did not (p = 0.028). These data are consistent with the possibility of the airborne spread of a virus.
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Psychiatrically hospitalized adolescents from city and voluntary services who had been diagnosed as having conduct disorder were compared with psychiatrically hospitalized adolescents who had never been so diagnosed. There were no significant symptomatic differences. The major factor distinguishing adolescents ever diagnosed as having conduct disorder was violence, regardless of other symptoms. The most common discharge diagnosis of those who had formerly been diagnosed as having conduct disorder was schizophrenia. However, even violence did not distinguish those discharged with a diagnosis of conduct disorder from those whose diagnoses were subsequently changed. With its focus on manifest behaviors and its lack of clear exclusionary criteria, the conduct disorder diagnosis obfuscates other potentially treatable neuropsychiatric disorders.
We studied the suppressor activity and surface-membrane antigens of immunoregulatory neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia. The neoplastic T cells were potent inhibitors of immunoglobulin production by pokeweed-mitogen-stimulated normal B cells when radiosensitive cooperative normal T cells were present. Preculturing the leukemic cells with normal T cells or soluble factors allowed them to mediate suppression without the need for cooperating T cells. While acquiring new functional capabilities, approximately 95 per cent of the leukemic cells displayed an antigen (OKT-3) that is found on mature normal T cells; 77 per cent displayed an antigen (Tac) that is found on normal activated immunoregulatory effector cells but not on thymocytes or circulating T cells that are precursors of these effector cells. The results suggest that a population of leukemic prosuppressor cells can be induced to undergo both functional and antigenic differentiation by the influence of normal T cells.
To characterize the suppressor activity of neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia, we applied an in vitro assay that determines the capacity of pokeweed-mitogen-stimulated lymphocytes to mature into immunoglobulin-secreting cells. The geometric mean synthesis by peripheral blood lymphocytes from 12 normal persons was 3200 ng for IgM, 2447 ng for IgG and 1825 for IgA (2 X 10(6) cells per 12 days in culture). The patient's leukemic cells produced no detectable immunoglobulin and depressed the immunoglobulin production of normal lymphocytes by 85 to 100 per cent in co-culture experiments. However, suppression was observed only when co-operating normal T cells were present. Prior irradiation of either the leukemic T cells or the co-operating normal T cells nullified the suppressor effect. Therefore, an interaction between at least two different T-cell subsets may be required for the generation of suppressor effector T cells in man.