Organ-Specific Hematopoietic Changes Induced by a Recombinant Human Interferon-{alpha} in Mice

Organ-Specific Hematopoietic Changes Induced by a RecombinantHuman Interferon- in Mice. ROSENTHAL, G. J., STRANAHAN, R. P.,ILL, THOMPSON, M., BLAIR, P., GERMOLEC, D. R., COMMENT, C. E.,SCHWAB, K., AND LUSTER, M. I. (1990). Fundam. Appl. Toxicol.14, 666–675. Interferon-a (IFN-) is a naturally occurringcytokine that mediates numerous biological activities and hasdemonstrated therapeutic potential in a variety of malignancies.Encouraging activity against HIV-1 replication has also beenobserved with IFN- in the treatment of AIDS, although hematotoxicityhas been a frequently observed side effect. In addition, invitro studies have suggested that IFN- may function as a down-regulatorof myelopoiesis. A recombinant hybrid of subtypes of human IFN-,rHuIFN-A/D, has antiviral activity in mu-rine cells in vitroand In vivo. This study examines the effect of acute and subchronicexposure to rHuIFN-A/D on hemopoietic and immune parametersin C57B1/6 mice. IFN-a was administered ip at 0, 1000, 10,000,and 100,000 units/day for either 1 or 10 consecutive days. Manyof the known effects of IFN- in humans such as anemia, leukopenia,and thrombocytopenia were observed in mice following subchronicexposure, with the latter two effects also manifested followingacute exposure. Further analysis showed that this leukopeniawas not selective. Both splenic and bone marrow cells were examinedfollowing 10 days of dosing with the high dose of IFN-. Lymphocyteswere reduced in both compartments, while granulocytes were increasedin both compartments. Bone marrow cells programmed to differentiateinto granulocytes (CFU-G) were suppressed, while macrophageprogenitors (CFU-M) were stimulated. Erythroid cells decreasedin the marrow but increased in the spleen, suggesting that themicroenvironmerit may play a significant role in the effectof IFN-. The proliferative capacity of both B and T spleniclymphocytes was significantly suppressed in a dose-related fashionfollowing multiple exposure to IFN-a. Clinically, IFN-a is mostoften given in multiple doses and the present data suggest thatsuch a regimen is toxic to both erythroid and myeloid cells,as well as being immunotoxic to splenic B and T lymphocytes.     

Postpartum Exercise and Food Intake: The Importance of Behavior-Specific Self-efficacy

Objective To examine the relationships between psychosocial characteristics and change in exercise and food intake of women during the first year postpartum.

Design A prospective cohort study following women from pregnancy until 1 year postpartum. Psychosocial variables, change in food intake, and exercise frequency were assessed using anonymous mailed questionnaires during pregnancy and at 1 year postpartum. Sociodemographic and anthropometric information was obtained from the medical record.

Subjects/setting Six hundred twenty-two women who enrolled for prenatal care in the Bassett Healthcare system between November 7, 1994, and November 15, 1996, and who met the eligibility criteria. The attrition rate for completing the questionnaire at 1 year postpartum was 20%.

Statistical analyses performed Multivariate linear regression with exercise frequency at 1 year postpartum and change in food intake during the second 6 months postpartum as the dependent variables and psychosocial factors assessed at 1 year postpartum as the independent variables, controlling for sociodemographic variables, body mass index, and gestational weight gain.

Results Higher exercise self-efficacy and having the intention to exercise were associated with more frequent exercise at 1 year postpartum in the multivariate regression analysis (r²=20%). Food intake self-efficacy, body satisfaction, weight gain acceptance, and drive for thinness were all significant in the multivariate analysis (r²=7%) and higher scores on these variables were associated with reductions in food intake.

Applications/conclusions Interventions that aim to help women get regular exercise and make appropriate reductions in food intake during the postpartum period should focus on self-efficacy specific to the targeted behaviors. For example, dietitians may strengthen exercise self-efficacy by providing postpartum women with mastery experiences of setting realistic exercise goals. Likewise, dietitians can focus on food intake self-efficacy by modeling strategies that women can use to avoid overeating in stressful situations. J Am Diet Assoc. 2001;101:1430-1437.     

Does preterm birth affect global and configural processing differently?

Aim We investigated whether preterm birth affects later visuocognitive function and, in particular, whether it affects global and configural perceptual processing differently. Method We compared the performance of 21 healthy preterm children (8 females, 13 males; mean age 7y 8mo, SD 8mo; mean gestational age 29.3wks, SD 1.9; mean birthweight 1186.5g, SD 377.2) with that of a matched term comparison group (8 females, 13 males; mean age 7y 11mo, SD 1y 1mo; mean gestational age >37wks; mean birthweight >2500g) in two perceptual tasks pinpointing differences between local and global and between local and configural processing. Results There was no difference between preterm and term children’s global processing, as both groups showed a bias towards global information (preterm: t[1,20]=2.6, p=0.01; comparison group: t[1,20]=3.0, p=0.01). By contrast, no such typical pattern of performance was found for configural processing as, unlike the comparison group (t[1,20]=7.1, p<0.001), preterm children preferentially relied on local rather than on configural information (t[1,20]=?15.4, p<0.001). Interpretation These findings suggest that preterm birth may have a greater influence on the development of later perceptual skills than originally envisaged. We discuss the results according to the current and dominant view of the visual system.     

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n =75) or with additional cyclophosphamide, C-VAMP ( n =129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1–11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P =0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.