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Biomedical subjects

C L Miller

Publications and source records attributed to C L Miller.

At least 127 records · Page 7Linked to original sources

Assessment of inactivated influenza-A vaccine after three outbreaks of influenza A at Christ's Hospital.

The boys of Christ's Hospital experienced outbreaks of influenza A in 1972 (A/England/42/72), in 1974 (A/Port Chalmers), and in 1976 (A/Victoria). In each outbreak, the protective effect of inactivated influenza-A vaccine was limited to those boys, not already immune, who were vaccinated for the first time with the most up-to-date strain. Revaccination with the same strain did not increase the degree of protection, and revaccination with a later strain did not afford protection against subsequent challenge. The cummulative attack-rate in the three outbreaks was similar in all groups irrespective of vaccination history. These observations suggest that annual revaccination with inactivated influenza-A vaccine confers no long-term advantage.

Adolescent↗

Predicting fatal sepsis in burn patients.

The high morbidity after severe thermal insult is believed to be related partially to a resultant decrease in immunocompetence. We tested the ability of phytohemagglutinin (PHA) and Concanavalin (Con A) to stimulate lymphocyte transformation in 17 patients with moderate to severe thermal injury (greater than 25% BSA). The patients acted as their own controls and the per cent change in their mitogen response was measured over time. Eight acutely burned patients who subsequently developed severe sepsis (Group I) had decreased ability (mean, 12% of normal) to proliferate in response to PHA, and six of these died of severe sepsis. The depressed response appeared 4 to 7 days postinjury and predated clinical evidence of sepsis by 2 to 4 days. Cells from four patients who had mild infectious complications (Group II) demonstrated greatly augmented mitogen responses (mean + 243%) approximately 7 to 10 days postinjury. Five burn patients whose clinical course was sepsis free (Group III) exhibited only minimal changes in their mitogen responses (mean +30%). Although the Con A responses of the patients' cells corresponded less to their pathology, Group I patients whose cells exhibited depressed PHA responsiveness also had diminished Con A responses. Group II patients' cells also showed increases in Con A-induced stimulation. Group III patients, who had only slightly augmented PHA responses, had minimal decreases of the Con A-induced lymphocyte transformation. Many severely burned patients develop septicemia as a result of their large wound surfaces. The appearance of decreases in mitogen-induced proliferation, however, appears to characterize those patients who will be unable to handle the septic challenge.

Adult↗

Selective adaptation effects in infant speech perception paradigms.

The present studies were conducted to explore the possible role of selective adaptation in infant speech perception. In the first study, in which the growth of adaptation was examined by presenting adult listeners with successive blocks of 20 repeating stimuli, reliable adaptation effects were observed after only 80 stimulus presentations. In addition, recovery following adaptation was relatively rapid and complete by the end of a postadaptation identification sequence. Experiment II constituted a more direct investigation of the possible role of adaptation in infant speech perception in which actual protocols from heart-rate (HR) and non-nutritive high-amplitude sucking (HAS) infant testing sessions were presented to adult listeners. Reliable adaptation effects were obtained within the HAS protocol, but not within the HR format. This pattern of results was consistent with that observed in experiment I. The implications of these adult adaptation results for the processes underlying the infant's responsiveness to these stimulis were discussed.

Adult↗

Changes in lymphocyte activity after thermal injury. The role of suppressor cells.

The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients.

Adult↗

Sequential observations of in vitro responses of lymphocytes to phytohemagglutinin in patients receiving gold therapy for rheumatoid arthritis.

Forty-seven patients receiving gold therapy for rheumatoid arthritis were observed sequentially at 6-monthly intervals. When the disease was in remission, and remained so, the in vitro responses of lymphocytes to phylohemagglutinin stimulation tended to be normal. Improvement in the disease were associated with improvement in lymphocyte response and deterioration associated with depression of response. Our observations suggest that these changes are a reflection of disease activity and their relationship to gold therapy is indirect.

Arthritis, Rheumatoid↗

Effect of gold salts on adherent mononuclear cells in tissue culture.

Adherent mononuclear cells from normals and patients with rheumatoid arthritis (RA) were isolated and effects of gold salts on cell cultures assessed in vitro. Phagocytic function of adherent mononuclear cells was assessed by the injestion of opsonized chicken red blood cells. Absolute numbers of phagocytic cells were higher in the RA patients than normals. Gold salts in concentrations 0.5-5.0 microgram/ml significantly reduced the numbers of both adherent and phagocytic cells when compared to control cultures. This suppression was particularily marked in the RA patients and was dose and time dependent. However, mononuclear cells surviving incubation with gold salts appeared to maintain phagocytic function in similar proportions to control cultures.

Arthritis, Rheumatoid↗

Effects of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, and L-phenylalanine mustard on B16, Cloudman S91, and Harding-Passey mouse melanomas.

The effects of 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), and L-phenylalanine mustard (L-PAM) have been compared by using three i.p. transplanted mouse melanomas: the B16 melanoma in C57BL/6 mice; the Harding-Passey (HP) malanoma in BALB/c X DBA/2F1 (hereafter called CD2F1) mice; and the Cloudman S91 melanoma in DBA/2 mice. HP melanoma responds well to all three drugs. S91 responds only to L-PAM and MeCCNU. DTIC may accelerate death in mice bearing this tumor. B16 responds well to L-PAM and moderately well to MeCCNU and to multiple injections of DTIC. The best response to DTIC and MeCCNU is given by HP, while the best response to L-PAM is given by S91. Tumor cell-doubling times were found to be 1.5 days for B16, 2 DAYS FOR HP, and 3 days for S91. HP would seem to be the most responsive malanmoma with respect to the 3 agents studied. This may be due to an interaction between the chemotherapeutic agents and the host immune response, since the HP tumor arose in a noninbred mouse and is thus nonsyngeneic with the CD2F1 host. All three tumors appear to be interesting biological models for studying drug combinations and combined therapeutic modalities against melanoma.

Animals↗