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Biomedical subjects

S B Campbell

Publications and source records attributed to S B Campbell.

At least 19 recordsLinked to original sources

CD4 ligation promotes the IL-4-independent development of IL-4-producing clones from naive CD4(+) T cells.

The signals that trigger IL-4-independent IL-4 synthesis by conventional CD4(+) T cells are not yet defined. In this study, we show that coactivation with anti-CD4 mAb can stimulate single naive CD4(+) T cells to form IL-4-producing clones in the absence of APC and exogenous IL-4, independently of effects on proliferation. When single CD4(+) lymph node cells from C57BL/6 mice were cultured with immobilized anti-CD3epsilon mAb and IL-2, 65-85% formed clones over 12-14 days. Coimmobilization of mAb to CD4, CD11a, and/or CD28 increased the size of these clones but each exerted different effects on their cytokine profiles. Most clones produced IFN-gamma and/or IL-3 regardless of the coactivating mAb. However, whereas 0-6% of clones obtained with mAb to CD11a or CD28 produced IL-4, 10-40% of those coactivated with anti-CD4 mAb were IL-4 producers. A similar response was observed among CD4(+) cells from BALB/c mice. Most IL-4-producing clones were derived from CD4(+) cells of naive (CD44(low) or CD62L(high)) phenotype and the great majority coproduced IFN-gamma and IL-3. The effect of anti-CD4 mAb on IL-4 synthesis could be dissociated from effects on clone size since anti-CD4 and anti-CD11a mAb stimulated formation of clones of similar size which differed markedly in IL-4 production. Engagement of CD3 and CD4 in the presence of IL-2 is therefore sufficient to induce a substantial proportion of naive CD4(+) T cells to form IL-4-producing clones in the absence of other exogenous signals, including IL-4 itself.

Animals↗

A prospective crossover trial comparing intermittent intravenous and continuous oral iron supplements in peritoneal dialysis patients.

BACKGROUND: Concomitant iron supplementation is required in the great majority of erythropoietin (Epo)-treated patients with end-stage renal failure. Intravenous (i.v.) iron supplementation has been demonstrated to be superior to oral iron therapy in Epo-treated haemodialysis patients, but comparative data in iron-replete peritoneal dialysis (PD) patients are lacking. METHODS: A 12-month, prospective, crossover trial comparing oral and i.v. iron supplementation was conducted in all Princess Alexandra Hospital PD patients who were on a stable dose of Epo, had no identifiable cause of impaired haemopoiesis other than uraemia, and had normal iron stores (transferrin saturation >20% and serum ferritin 100-500 mg/l). Patients received daily oral iron supplements (210 mg elemental iron per day) for 4 months followed by intermittent, outpatient i.v. iron infusions (200 mg every 2 months) for 4 months, followed by a further 4 months of oral iron. Haemoglobin levels and body iron stores were measured monthly. RESULTS: Twenty-eight individuals were entered into the study and 16 patients completed 12 months of follow-up. Using repeated-measures analysis of variance, haemoglobin concentrations increased significantly during the i.v. phase (108+/-3 to 114+/-3 g/l) compared with each of the oral phases (109+/-3 to 108+/-3 g/l and 114+/-3 to 107+/-4 g/l, P<0.05). Similar patterns were seen for both percentage transferrin saturation (23.8+/-2.3 to 30.8+/-3.0%, 24.8+/-2.1 to 23.8+/-2.3%, and 30.8+/-3.0 to 26.8+/-2.1%, respectively, P<0.05) and ferritin (385+/-47 to 544+/-103 mg/l, 317+/-46 to 385+/-47 mg/l, 544+/-103 to 463+/-50 mg/l, respectively, P=0.10). No significant changes in Epo dosages were observed throughout the study. I.v. iron supplementation was associated with a much lower incidence of gastrointestinal disturbances (11 vs 46%, P<0.05), but exceeded the cost of oral iron treatment by 6.5-fold. CONCLUSIONS: Two-monthly i.v. iron infusions represent a practical alternative to oral iron and can be safely administered to PD patients in an outpatient setting. Compared with daily oral therapy, 2-monthly i.v. iron supplementation in PD patients was better tolerated and resulted in superior haemoglobin levels and body iron stores.

Administration, Oral↗

Infant affective responses to mother's still face at 6 months differentially predict externalizing and internalizing behaviors at 18 months.

This study investigated (a) stability and change in infant affective responses to the still-face interaction, (b) whether maternal depression affected infant responses, and (c) whether responses to the still-face interaction predicted toddler problem behaviors. Infants (63 girls and 66 boys) of European American mothers (67 depressed and 62 nondepressed) were observed in the still-face interaction at 2, 4, and 6 months. Affect and gaze were coded on a 1-s time base. There were stable individual differences in gazing away and in rates of negative affect. Developmental change occurred only for gazing away, which increased. At 18 months, infants who failed to smile at 6 months in the still-face interaction showed more externalizing-type behaviors than did other toddlers. Infants who failed to cry at 6 months showed fewer internalizing-type behaviors. Mothers' current depressive symptoms and infants' earlier responses to the still-face interaction made independent, comparable contributions to problem behaviors at 18 months.

Adult↗

Oral versus intravenous iron supplementation in peritoneal dialysis patients.

The vast majority of erythropoietin (EPO)-treated peritoneal dialysis (PD) patients require iron supplementation. Most authors and clinical practice guidelines recommend primary oral iron supplementation in PD patients because it is more practical and less expensive. However, numerous studies have clearly demonstrated that oral iron therapy is unable to maintain EPO-treated PD patients in positive iron balance. Once patients become iron-deficient, intravenous iron administration has been found to more effectively augment iron stores and hematologic response than does oral therapy. We recently performed a prospective, cross-over trial in 28 iron-replete PD patients and showed that twice-monthly outpatient iron polymaltose infusions (200 mg) were a practical and safe alternative to oral iron. That treatment produced significant increases in hemoglobin concentration and body iron stores. The additional expense of intravenous iron therapy was completely offset by reductions in EPO dosage. Careful monitoring of iron stores is important in patients receiving intravenous iron supplementation in view of epidemiologic links with infection and cardiovascular disease. Nevertheless, a growing body of evidence suggests that, as has been found for hemodialysis patients, intravenous iron therapy is superior to oral iron supplementation in EPO-treated PD patients.

Administration, Oral↗

Early externalizing behavior problems: toddlers and preschoolers at risk for later maladjustment.

The early emergence and developmental implications of externalizing behavior problems in toddlers and preschoolers are discussed with an emphasis on which young children are truly at risk for continuing problems. The extant literature is reviewed with a focus on the stability of early externalizing behavior and the diverse pathways that young children, primarily boys, with early-emerging problems may follow. Findings from a number of studies, both epidemiological and high risk, suggest that the small subgroup of boys with multiple risk factors that include especially high levels of early hyperactivity and aggression, and high levels of negative parenting and family stress, are most likely to evidence continuing problems at school entry. Sociodemographic and neighborhood influences are also discussed, as are implications for future research and policy.

Adjustment Disorders↗

Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes.

A simple culture system devoid of antigen-presenting cells was used to examine the ability of immobilized antibodies to lymphocyte function-associated antigen-1 (LFA-1) (CD11a), CD28 and CD4 or CD8 to modulate the responses of normal murine CD4+ and CD8+ lymph node T cells to immobilized anti-CD3 antibody and interleukin-2 (IL-2). All the antibodies enhanced proliferative responses to limiting anti-CD3 antibody. Both CD4+ and CD8+ cells produced substantial titres of IL-3 and interferon-gamma (IFN-gamma) in primary and secondary cultures regardless of the coactivating antibodies used for priming. By contrast, the combination of anti-CD4 with anti-CD3 antibody stimulated significantly higher titres of IL-4 than any other antibody combination in cultures of CD4+ cells. This CD4-dependent IL-4 response was induced in CD4+ T cells of naive (CD44low) phenotype and was similar in magnitude to the response induced by exogenous IL-4 but, unlike the latter, was not associated with elevated IL-3 synthesis. A comparable effect of anti-CD8 antibodies on CD8+ cells was not observed: although IL-4 production by CD8+ cells was induced by exogenous IL-4, it was not detected following coactivation with anti-CD8 or any other antibodies. We conclude that anti-CD4 antibody is a potent inducer of IL-4-secreting CD4+ T cells whose effects can be distinguished from those of anti-CD8 antibody on CD8+ T cells and from those of IL-4 on either subset.

Animals↗

Diagnostic status and symptomatic behavior of hard-to-manage preschool children in middle childhood and early adolescence.

Followed 2 cohorts of hard-to-manage preschool children and comparison children without early problems to middle childhood and early adolescence. Children with early problems, especially problems that were still evident at school entry, were more likely to meet diagnostic criteria for an externalizing diagnosis at follow-up. Hard-to-manage children in Cohort 1 with problems that persisted from ages 3 through 9 years were much more likely to meet diagnostic criteria at age 13 than children whose early problems were less stable in elementary school. Similarly, hard-to-manage boys in Cohort 2 whose problems persisted at age 6 were more likely to meet criteria for an externalizing diagnosis at age 9 than hard-to-manage boys whose problems appeared less stable at age 6. Across cohorts, children with persistent problems had higher levels of symptoms and more varied symptoms at ages 3 and 4 and over the course of development.

Adolescent↗

Inattention, impulsivity, and hyperactivity from preschool to school age: performance of hard-to-manage boys on laboratory measures.

Boys identified as hard-to-manage at age 4 and age-matched controls were assessed on laboratory measures of inattention, impulsivity, and hyperactivity at ages 4, 6, and 9. Hard-to-manage boys still exhibited some behavioral difficulties at age 9, but were not more inattentive or impulsive than controls. Boys with Attention Deficit Disorder (ADD) at age 9 showed performance deficits in each symptom-related domain relative to problem boys without ADD and controls. However, hard-to-manage problem boys with and without ADD did not differ on most earlier measures of inattention, impulsivity, and hyperactivity, suggesting that symptoms specific to ADD emerged more clearly between ages 6 and 9.

Attention Deficit Disorder with Hyperactivity↗

Mothers' affective behavior with infant siblings: stability and change.

To evaluate within-family differences in maternal affective behavior toward siblings, face-to-face interactions were observed between 39 mothers and their firstborn and second-born infants at 2 months of age. Mother and infant affect was coded on a 1-s time base with behavioral descriptors. Mothers were more positive with second-born infants, and second-born infants were more positive than were firstborns. The siblings' affective behaviors were unrelated, but maternal positive affect was both moderately stable between siblings and correlated with each infant's affect. Thus, in the context of stable individual differences in maternal positive affect, siblings experienced unique affective interactions with their mothers as early as 2 months.

Adult↗

A non-invasive continuous method of measuring blood volume during haemodialysis using optical techniques.

Hypotension during haemodialysis and fluid overload between treatments are major problems for haemodialysis patients. Clinical means of assessing hydration state can be relatively imprecise. We describe a non-invasive method of measuring absolute blood volume (BV) during a mock in vitro haemodialysis session which adds objective information to that assessment. As fluid is removed by ultrafiltration, haemoglobin concentration [Hb] rises proportionately with the fall in BV. An optical monitor clamped across the transparent dialysis tubing gives a continuous readout of near infra-red light transmitted through the blood, and this can be converted to [Hb] values. The net change in BV is the difference between the volume of fluid ultrafiltered and the volume which refills the vascular compartment from the extravascular space. By analysing the change in [Hb] and therefore the change in BV at two different rates of fluid removal, the absolute BV can be determined. The accuracy of this method was tested in vitro. This optical method accurately measures the change in BV over a range of [Hb] from 4 to 15 g/dl and blood circulation pump speeds of 150-300 ml/min. A series of 10 in vitro experiments was performed. The mean relative difference between the measured BV and the calculated BV, was 5.7 +/- 2.5%. This readily repeatable technique can accurately measure BV during a mock in vitro haemodialysis session, thus providing information for the clinical assessment of the hydration state. Information from these experiments will assist in future in vivo studies.

Biomedical Engineering↗

Recovery of gastrointestinal function after renal transplantation in a patient with sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis.

We describe the rapid and dramatic improvement in gastrointestinal function that occurred after successful renal transplantation in a women with severe sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis (CAPD). We postulate that the antiinflammatory effect of the immunosuppressive agents was the most important factor leading to the patient's recovery.

Adult↗

Behavior problems in preschool children: a review of recent research.

Research on the prevalence, course, and correlates of behavior problems in preschool children was examined. Prospective epidemiological studies and follow-up studies of clinical/high risk samples indicate that serious externalizing problems identified early often persist. Negative, inconsistent parental behavior and high levels of family adversity are associated with the emergence of problems in early childhood and predict their persistence to school age. Studies are examined from a developmental perspective and integrated with research on optimal parent-child relationships. The severity of initial problems and family context are related to different developmental outcomes.

Child↗

Hard-to-manage preschool boys: externalizing behavior, social competence, and family context at two-year followup.

Boys, identified as hard to manage in preschool, were followed up 2 years after initial assessment. Mothers, fathers, and teachers continued to rate hard-to-manage boys as having more problems with attention and impulse control, and as more oppositional, than comparison boys who had been problem-free at intake; problem boys also were rated as less socially competent by all three informants. Differences in severity were apparent as a function of initial referral source. Boys identified as showing significant problems by at least two informants (28% of the problem boys) were especially low in social competence and their mothers reported more symptoms of depression and parenting stress. Family adversity, lower IQ, and severity of symptoms at intake discriminated boys with continuing problems from those with less serious difficulties at followup. Control boys with potentially emerging problems were characterized by more family problems than the remaining control boys. Implications for the development of problems in young children are discussed.

Child↗

Increased skeletal uptake of Tc-99m methylene diphosphonate in milk-alkali syndrome.

A case of milk-alkali syndrome is described in a 34-year-old man taking an over-the-counter antacid preparation for gastroesophageal reflux. A Tc-99m MDP bone scan performed in the initial investigation of the hypercalcemia was markedly abnormal with a "metabolic" pattern of tracer uptake similar to that seen in hyperparathyroidism and humoral hypercalcemia. Following withdrawal of the antacid and calcium, the bone scan appearance returned to normal, as did the biochemical markers of his disease.

Animals↗

Hard-to-manage preschool boys: symptomatic behavior across contexts and time.

Preschool boys identified by their parents and/or teachers as active, inattentive, and impulsive (N = 69) at age 4 were compared with boys without problems (N = 43) on observational measures of symptom-related behaviors, obtained across contexts (home, laboratory, and preschool). Problem boys differed from comparison boys on measures of activity/inattention, noncompliance, and impulsivity obtained in the 3 settings. At a 2-year follow-up, when they were 6 years old, problem boys continued to differ from comparison boys on laboratory measures of activity and impulsivity; there also was some stability in these symptomatic behaviors. Implications of these findings for the emergence and persistence of externalizing problems in preschool boys are addressed.

Aggression↗

Hard-to-manage preschool boys: family context and the stability of externalizing behavior.

Preschool boys identified by their teachers as active, inattentive, and impulsive (N = 42) were compared with matched classroom controls (N = 43) and with parent-identified problem boys (N = 27) on measures of family functioning often associated with children's problem behaviors, including family history of psychopathology, stressful life events, and family composition. Teacher-identified and parent-identified problem boys did not differ on measures of family adversity, and both groups came from less well functioning families than comparison boys. Mothers of problem boys, regardless of referral source, were more negative and controlling toward their sons when observed in a compliance task. Children's problem behaviors were moderately stable over a one-year follow-up period; initial symptom levels, maternal self-reported depression, and negative maternal control predicted follow-up ratings of externalizing problems.

Child Behavior Disorders↗

Prevalence and correlates of postpartum depression in first-time mothers.

The prevalence and correlates of postpartum depression were examined in a large (N = 1,033) sample of married, primiparous, middle-class mothers of full-term, healthy infants; 9.3% met modified Research Diagnostic Criteria for depression. However, 39% of the nondepressed women also reported at least 1 somatic symptom. Depressed women whose symptoms were current obtained elevated scores on the Center for Epidemiological Studies-Depression scale, as did some women who did not meet depression criteria. Depressed women different from nondepressed women on several socioeconomic status indicators and the occurrence of obstetric complications, even in this low-risk sample. These data have implications for the assessment of depression in postpartum women.

Adult↗