Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.

BACKGROUND: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. PATIENTS AND METHODS: The doses of cilengitide were 600 or 1200 mg/m(2) as a 1-h infusion twice weekly every 28 days. A novel dose escalation scheme was utilized that relied upon the biological activity rate. RESULTS: Twenty patients received 50 courses of cilengitide with no dose-limiting toxic effects. The pharmacokinetic (PK) profile revealed a short elimination half-life of 4 h, supporting twice weekly dosing. Of the six soluble angiogenic molecules assessed, only E-selectin increased significantly from baseline. Analysis of tumor microvessel density and gene expression was not informative due to intrapatient tumor heterogeneity. Although several patients with evaluable tumor biopsy pairs did reveal posttreatment increases in tumor and endothelial cell apoptosis, these results did not reach statistical significance due to the aforementioned heterogeneity. CONCLUSIONS: Cilengitide is a well-tolerated antiangiogenic agent. The biomarkers chosen in this study underscore the difficulty in assessing the biological activity of antiangiogenic agents in the absence of validated biological assays.

Cost-effectiveness of lifestyle and structured exercise interventions in sedentary adults: results of project ACTIVE.

BACKGROUND: Project ACTIVE was a randomized clinical trial comparing two physical activity interventions, lifestyle and traditional structured exercise. The two interventions were evaluated and compared in terms of cost effectiveness and ability to enhance physical activity among sedentary adults. DESIGN: This was a randomized clinical trial. SETTING/ PARTICIPANTS: The study included 235 sedentary but healthy community-dwelling adults. INTERVENTION: A center-based lifestyle intervention that consisted of behavioral skills training was compared to a structured exercise intervention that included supervised, center-based exercise. MAIN OUTCOME MEASURES: The main outcome measures of interest included cost, cardiorespiratory fitness, and physical activity. RESULTS: Both interventions were effective in increasing physical activity and fitness. At 6 months, the costs of the lifestyle and structured interventions were, respectively, $46.53 and $190.24 per participant per month. At 24 months these costs were $17.15 and $49.31 per participant per month. At both 6 months and 24 months, the lifestyle intervention was more cost-effective than the structured intervention for most outcomes measures. CONCLUSIONS: A behaviorally-based lifestyle intervention approach in which participants are taught behavioral skills to increase their physical activity by integrating moderate-intensity physical activity into their daily lives is more cost-effective than a structured exercise program in improving physical activity and cardiorespiratory health. This study represents one of the first attempts to compare the efficiency of intervention alternatives for improving physical activity among healthy, sedentary adults.

Breast cancer. Making the diagnosis.

The approach to women with breast complaints must be individualized based on the presenting problem, patients' age, and the degree of clinical suspicion. Needle-biopsy, techniques are often cost-effective. In patients with suspicious breast abnormalities, a thorough imaging workup facilitates the selection of definitive local therapy.

Role conflict and rapid socio-economic change: breastfeeding among employed women in Thailand.

Conflicts between women's productive and reproductive roles are intensified by rapid development and social change. Women have a right to offer optimum nutrition to their babies through breastfeeding; they also are entitled to seek gainful employment. For many, furthermore, employment is essential to the economic survival of their families. This article derives from a combined qualitative and quantitative study conducted in Chiang Mai, Thailand. Interviews were carried out with 313 women to investigate the experiences of those who resumed employment within six months after delivery. The findings demonstrate that urban women in the modern workplace face many obstacles in their efforts to maintain lactation while simultaneously undertaking paid work. Current public policies do not address these obstacles effectively, which is of particular concern in today's volatile economic climate.

Environmental endocrine disruption: an effects assessment and analysis.

This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

Breastfeeding in Vietnam: poverty, tradition, and economic transition.

Breastfeeding's crucial role in infant health is almost universally recognized. Although nearly all Vietnamese women initiate breastfeeding and duration is lengthy, infant growth faltering and malnutrition are widespread. Based on an analysis of in-depth interviews, observation in hospitals, and the available literature, the paper argues that complacency about breastfeeding in Vietnam is unwarranted. Discussion focuses on the principal influences on infant feeding in Vietnam, among them poverty, rapid socio-economic change, marketing by formula manufacturers, and some traditional perceptions about childbirth. The conclusion considers possible directions for breastfeeding promotion to address these multiple influences.

Development of public policy and physical activity initiatives internationally.

Epidemiological, pathological, clinical, and experimental studies over the past 40 years convincingly show that physical inactivity and low physical fitness contribute substantially to the major chronic diseases prevalent in industrialised societies. Several industrialised countries around the world report increases in physical activity participation among adults in recent years, but the prevalence of inactivity remains high. These increases in voluntary exercise are at least partially offset by decreasing daily energy demands due to increased mechanisation at home, at work and during leisure-time. In developing countries, physical inactivity is becoming a prevalent lifestyle due to rapid social and economic changes. Clinical interventions and mass appeals to be more physically active are limited in effectiveness against the background of increasingly sedentary lifestyles. Exercise scientists and public health officials need to turn attention to public policy and legislative initiatives to restructure physical and social environments to encourage more physical activity and discourage sedentary habits.

When can stereotactic core biopsy replace excisional biopsy?--A clinical perspective.

Stereotactic core biopsy is becoming increasingly popular as a technique which provides a histologic diagnosis for mammographic abnormalities while avoiding the trauma, deformity, and much of the cost associated with surgical biopsy. This review evaluates the published literature on the diagnostic accuracy of core biopsy for ductal carcinoma in situ and invasive breast cancer and the ability of core biopsy to characterize malignant lesions sufficiently to allow treatment planning. Issues of cost effectiveness are examined in the context of the degree of suspicion of the mammographic abnormality being sampled by core technique as well as subsequent breast cancer therapy.

Saving for hospital care costs in Singapore: are there lessons for Australia? [corrected].

Australian political leaders and policy analysts have increasingly sought to learn from Singapore, a nation which, despite its small size and lack of natural resources, has enjoyed rapid economic growth. Of particular interest to Australian policymakers has been Singapore's compulsory superannuation system, which has provided high levels of domestic savings and high levels of home ownership; it has also incorporated a scheme to enable Singaporeans to save for the costs of health care. In this article, Singapore's Medisave policy is described within its broader socioeconomic context. Saving for health care costs has been a largely neglected option in recent policy debate about reforming funding arrangements for hospital care in Australia. The potential for a formalised scheme for medical savings in Australia, subsidised by taxation concessions, is explored in terms of its socioeconomic policy implications, its congruence with Australian values, and the logistical ramifications of such a scheme.

Health technologies for the developing world. Promoting self-reliance through improving local procurement and manufacturing capabilities.

To reduce their dependency on donors or the international currency costs of essential health care products, developing countries are building or improving capability for local manufacturing or competitive international procurement. Through long-term strategic planning, public/private partnerships, collaboration with firms in industrialized nations, and farsighted donor policies, the capacity for alternative supply can be increased in stages from importation through local processing and packaging to full production and multiproduct enterprises.

Medicare Physician Payment Reform: implications for nurse practitioners.

In January 1992, the federal government implemented a package of physician payment reforms for use in the Medicare program. Among these reforms is a resource-based fee schedule that replaces the customary, prevailing, and reasonable (CPR) method of payment that has been used since Medicare's inception. This article describes the recommendations of the Physician Payment Review Commission, a Congressional advisory group, concerning the implications of the resource-based fee schedule on nurse practitioners and other non-physician practitioners. Absent changes in current law, services provided by nurse practitioners will be paid based on the same formulas that were used under CPR. This author advises that these payment formulas be revised to reflect the differences in resource costs borne by physicians and nonphysicians. Furthermore, revisions to the payment formulas should be made in the near future before the Medicare fee schedule and the rules governing its use are adopted by other public (e.g., Medicaid) and private payers.

An assessment of variable thickness and fiber orientation of the skeletal muscle layer on electrocardiographic calculations.

This paper assesses the effectiveness of including variable thickness and fiber orientation characteristics of the skeletal muscle layer in calculations relating epicardial and torso potentials. A realistic model of a canine torso which includes extensive detail about skeletal muscle layer thickness and fiber orientation is compared with two other uniformly anisotropic models: one of constant thickness and the other of variable thickness. First, transfer coefficients are calculated from the model data. Then torso potentials for each model are calculated from the transfer coefficients and measured epicardial potentials. The comparison of calculated and observed torso potentials indicates that a simple model consisting of a uniformly anisotropic skeletal muscle layer of 1.0-1.5 cm constant thickness significantly improves the model. However, if photographic slices of the canine torso are used to introduce more detailed data about the variation in skeletal muscle thickness and fiber orientation into the model, the agreement and between calculated and measured torso potentials decreased, although a finite element mesh of over 5000 nodes was used to describe the skeletal muscle in the more detailed model. One source of error increase was considered to be due to numerical discretization and could be reduced with a much finer mesh or by utilizing higher order polynomials to represent the potential distribution within each finite element. However, the results presented in this paper show that high precision computation (64-bit word length) on the mainframe IBM 3081 with an attached FPS-164 gives a slow rate of improvement with reduced discretization intervals and that utilizing higher order polynomials within each finite element gives an even slower rate of improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Patient compliance with aggressive multimodal therapy in locally advanced breast cancer.

This study of compliance was performed to determine whether a medically indigent population with breast carcinoma that has been neglected is an appropriate group for inclusion in an aggressive combined treatment program. After incisional biopsy, 28 locally advanced breast cancer (LABC) patients received two cycles of cytoxan, Adriamycin, 5-Fluorouracil, and tamoxifen (CAFT) followed by a simple mastectomy and level I axillary dissection. After surgery, patients received four additional cycles of CAFT alternating with three cycles of 15 Gy to the chest wall and regional lymphatics. Compliance was defined as overall compliance, the percentage of patients completing the protocol as described; and appointment compliance, the ratio between treatments or appointments attended versus those scheduled. Overall compliance was 75% (21 of 28 patients). The total number of appointments scheduled was 1054 (mean, 37 +/- 2), and the total attended was 965 (mean, 34 +/- 3), giving an appointment compliance rate of 91.7%. Compliance did not vary significantly with age, marital status, nationality, the presence of complications, or delay to diagnosis. Compliance did decrease significantly with time. There was 100% overall compliance at 2 months, 82% at 6 months, and 75% at 1 year. We conclude that although our patients had neglected their disease and were medically indigent, they were highly motivated patients once in therapy. This suggests that complex treatment regimens are feasible as well as effective for the treatment of LABC.

Advances in sterilization equipment.

From the array of sterilization procedures that are safe, simple and effective, the service provider must select procedures that fit his or her logistical criteria, which include the cost and maintenance of equipment, availability of supplies, and training of the requisite personnel. In this paper, these criteria are discussed for each of the various sterilization procedures. Information about female sterilization equipment for conventional postpartum laparotomy, minilaparotomy, colpotomy, laparoscopy, and culdoscopy is presented, together with facts about the related tubal occlusion techniques. The standard ligation techniques for male sterilization are compared with the newer electrocoagulation and thermocoagulation methods. A variety of methods for both female and male sterilization that are in the research stage are also mentioned. It is concluded that, from a programmatic point of view, vasectomy and postpartum ligation via laparotomy are the optimal sterilization procedures. For women who have not recently been pregnant, minilaparotomy with a standard tubal ligation technique is recommended, except in large teaching hospitals where laparoscopy can be performed efficiently.