A breast feeding education and promotion program: Effects on knowledge,attitudes, and support for breast feeding

This study was undertaken to determine the effects of a partner-support, incentive-baed educational program on breast feeding knowledge, attitudes and support and to examine the relationship between feeding intentions and feeding behavior among low-income women. Women who expressed a willingness to participate in the intervention were randomly assigned to intervention and usual breast feeding (control) groups. Sixty-eight primipara women, with expected due dates between May and December, 1992, volunteered to participate in the study. Of these, 34 were randomly assigned to each of the two groups. Approximately 81 percent of the women completed the study, leaving n=29 in the control group and n-26 in the intervention group. The intervention consisted of special incentives (prizes) for women and their partners to participate in several breast feeding education and promotion activities. Intervention group women and their partners experienced positive changes in breast feeding knowledge and attitudes. Furthermore, the intervention seemed to have influenced more women in the treatment group to breast feed despite their prenatal feeding intentions. In addition, the partners of intervention group women were perceived to be more supportive of, breast feeding than control group partners. These findings suggest that incentives, such as donated prizes, can be used to attract lower socioeconomic group women and their partners to breast feeding promotion interventions. Participation in such interventions can produce positive changes in breast feeding knowledge, attitudes, and support, and can have a dramatic effect in promoting breast feeding.This study was supported through contract no. 59-3198-1-050 from the Food and Nutrition Service, U.S. Department of Agriculture.     

Differential inhibition and potentiation by cell-permeant analogues of cyclic AMP and cyclic GMP and NO-containing compounds of exocytosis in human neutrophils

Summary The chemoattractants, N-formyl-L-methio-nyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), complement C5a and platelet-activating factor (PAF), induce ß-glucuronidase release and aggregation and an increase in cytosolic Ca²⁺ [Ca²⁺]_i in human neutrophils. We studied the roles of cAMP and cGMP in neutrophil avtivation, using their cell-permeant analogues, N⁶,2-O-dibutyryl adenosine 3:5-cyclic monophosphate (Bt2cAMP) and N² ,2-O-dibutyryl guanosine 3:5-cyclic monophosphate (Bt₂cGMP) and the NO-containing compounds, sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1) and its prodrug, molsidomine (SIN-10). Bt₂cAMP, Bt₂cGMP, SIN-1 and SIN-10 but not SNP inhibited exocytosis induced by fMet-Leu-Phe. Superoxide dismutase potentiated the inhibitory effect of SIN-1. Bt₂cGMP and SNP potentiated C5a-induced ß-glucuronidase release, Bt₂cAMP, KCN, SIN-1 and SIN-10 being ineffective. KCN partially reversed the stimulatory effect of SNP, and in the presence of superoxide dismutase, SIN-1 potentiated C5a-induced exocytosis. PAF-induced ß-glucuronidase release was not affected by Bt₂cAMP, Bt₂cGMP, SNP and SIN-1. Bt₂cGMP was more effective than Bt2cAMP to inhibit aggregation and the increase in [Ca²⁺]_i induced by fet-Leu-Phe at submaximally effective concentrations. C5a-induced rises in [Ca²⁺]_i were not affected by Bt₂cAMP and Bt₂cGMP. Bt₂cAMP but not Bt₂cGMP inhibited the effect of PAF at submaximally effective concentrations on [Ca²⁺]_i. Our data suggest (I) that Bt2cGMP and Bt2cAMP differentially modulate neutrophil activation, that (II) NO-containing compounds partially mimick the effects of Bt₂cGMP on exocytosis and that (III) cGMP plays an inhibitory role in fMet-Leu-Phe- and a stimulatory role in C5a-induced ß-glucuronidase release. Send offprint requests to R. Seifert at the above address     

Antileishmanial action of Tephrosia purpurea linn,extract and its fractions against experimental visceral leishmaniasis

Tephrosia purpurea (family: Fabaceae), which is used in traditional remedies for the treatment of febrile attacks, enlargement and obstruction of liver, spleen, and kidney, was found to have significant antileishmanial activity, and has been extensively fractionated to locate the abode of activity. A fraction (F062) obtained from N‐butanol extract of T. purpurea showed consistent antileishmanial activity at 50 mg/ kg × 5 days by oral route against Leishmania donovani infection in hamsters. Activity was further confirmed in a secondary model, i.e., Indian langur monkeys (Presbytis entellus). Thus, the fraction F062 from this plant possesses potential to produce significant antileishmanial activity by oral route without producing any toxic side effects. Drug. Dev. Res. 60:285–293, 2003. © 2003 Wiley‐Liss, Inc.     

Computed tomography (CT) evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy—a feasibility study

Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8 Gy, 20 Gy/5#, 30 Gy/10# were: 128 (range 98–255), 141 (79–342), and 145 (65–235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy.     

Effects of whole body hyperthermia (41.8 degrees C) on the frequency of tumor cells in the peripheral blood of patients with advanced malignancies.

PURPOSE: Combining heat with antineoplastic drugs has produced evidence of antitumor synergism. An increasing number of trials are investigating whole body hyperthermia (WBH) in combination with chemotherapy in patients with advanced malignancies. Here we investigated whether the hyperdynamic state of the circulation as a consequence of WBH may stimulate dissemination of malignant cells. EXPERIMENTAL DESIGN: WBH in combination with chemotherapy was administered by a radiant heat device to 20 consecutive patients with advanced epithelial malignancies. One WBH session lasted for approximately 4 h (90 min heating time, 60 min plateau at 41.8 degrees C, and 60-80 min cooling). Peripheral blood was drawn before WBH treatment (baseline), at the end of the plateau (1 h), and 24 h and 48 h thereafter. After removal of leukocytes using anti-CD45 magnetic beads, circulating tumor cells were detected immunocytochemically using the monoclonal antibody A45-B/B3, which binds to a common epitope present on various cytokeratins. RESULTS: The method used to detect tumor cells in the peripheral blood proved to be specific and very sensitive (detection limit 1 tumor cell per 1.7 x 10(5) peripheral blood mononuclear cell). Before WBH, 6 of 20 patients had cyto-keratin-positive cells in their blood. A treatment-induced increase in the number of circulating tumor cells became statistically significant at 24 h after WBH (P = 0.043) and was detected in a total of 9 patients, 5 of whom had no detectable malignant cells at baseline. There was no evidence of a correlation between an increase in the number of circulating tumor cells and increased metastasis frequency. CONCLUSIONS: Our findings suggest that WBH might induce a temporary release of tumor cells into the circulation, but this spread appears to be clinically not significant in patients with advanced malignancies.     

Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance.

PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.     

Evidence-based health promotion for older people and instrumentalisation: comparing the influence of policy contexts in Austria and England

Health promotion (HP) amongst older people is an increasingly prominent policy concern for governments. The development of an evidence-base and the advocacy of effective interventions in the light of this act as legitimation tools for the overall HP phenomenon – assisting the growth of state and non-state funding for public health initiatives for older people. In structuring decision-making as to which individual projects/initiatives receive funding, frameworks for acknowledging efficacy impact on formats of HP work both positively and negatively. Drawing on recent research across the EU and focusing on the specific national contexts of Austria and England, this comparative policy analysis triangulates best-practice modelling, evaluation data and interviews with project coordinators to explore how policy contexts impact on the nature and format of HP interventions. Amidst a developing awareness of what effective practice looks like, successful HP initiatives must advocate their legitimacy within narrow rules of quality, where measurable outcomes have become the keys which unlock financial resources. Findings across both countries suggest that this instrumentalisation of legitimation, driven by economic pressures and bureaucratic generalisability, threatens the rationality of HP. From a Habermasian perspective, tensions emerge between projects’ remaining reflexive towards processes and their need to articulate the ‘success’ of the interventions in a language of outcomes. Over time, in an era where resources are increasingly scarce and competition over these intensifies, a danger exists whereby the instrumentality of HP begins to separate from, and impinge upon, the capacity for projects to think and act holistically.     

Managing the Impact of Immunogenicity in an Era of Immunotherapy: From Bench to Bedside

Biotherapeutics have revolutionized our ability to treat life-threatening diseases. Despite clinical success, the use of biotherapeutics has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs). The multifactorial nature of immunogenicity has prevented a standardized approach for assessing this and each of the assessment methods developed so far does not exhibit high enough reliability to be used alone, due to limited predictiveness. This prompted the Roche Pharma Research and Early Development (pRED) Immunogenicity Working Group to establish an internal preclinical immunogenicity toolbox of in vitro/in vivo approaches and accompanying guidelines for a harmonized assessment and management of immunogenicity in early development. In this article, the complex factors influencing immunogenicity and their associated clinical ramifications are discussed to highlight the importance of an end-to-end approach conducted from lead optimization to clinical candidate selection. We then examine the impact of the resulting lead candidate categorization on the design and implementation of a multi-tiered ADA/immunogenicity assay strategy prior to phase I (entry into human) through early clinical development. Ultimately, the Immunogenicity Toolbox ensures that Roche pRED teams are equipped to address immunogenicity in a standardized manner, paving the way for lifesaving products with improved safety and efficacy.