Search

Nonglucose carbohydrates such as mannose and inositol are important in early growth and development, although little is known about their metabolism. Our aim in this study was to determine the plasma appearance rates (Ra) for mannose and inositol in newborns as an index of utilization and as an improved guide to supplementation practices. We studied late-preterm (n = 9) and term (n = 5) infants (median 34 wk gestation, range 33-41 wk) using a multiple isotope infusion start time protocol to determine Ra for each carbohydrate. The plasma mannose concentration [median (range)] was 69.83 (48.60-111.75) micromol/L and the Ra was 0.59 (0.42-0.98) micromol x kg(-1) x min(-1) (854 micromol x kg(-1) x d(-1)). The plasma inositol concentration was 175.74 (59.71-300.60) micromol/L and Ra was 1.06 (0.33-1.75) micromol x kg(-1).min(-1) (1521 micromol x kg(-1) x d(-1)). The Ra for mannose and inositol are >10-fold higher than the amounts a breast-fed infant typically ingests, which are approximately 6 micromol x kg(-1) x d(-1) mannose and 150 micromol x kg(-1) x d(-1) inositol. Thus, for both mannose and inositol, the newborn infant must produce these compounds from glucose at rates sufficient to meet nutritional requirements.

Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.

Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting translation initiation in PI-IUGR liver. There was either no change (AMP activated kinase, mammalian target of rapamycin) or a paradoxical decrease (protein phosphatase 2A, eukaryotic initiation factor-2 alpha) in activation of major energy and cell stress sensors in PI-IUGR liver and skeletal muscle. A 13- to 20-fold increase in phosphoenolpyruvate carboxykinase and glucose 6 phosphatase mRNA expression in the PI-IUGR liver was-associated with a 3-fold increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha mRNA and increased phosphorylation of cAMP response element binding protein. Thus PI-IUGR is-associated with reduced branched chain amino acid uptake and growth factors, yet up-regulation of proximal insulin signaling and a marked increase in the gluconeogenic pathway. Lack of activation of several energy and stress sensors in fetal liver and skeletal muscle, despite hypoxia and low energy status, suggests a novel strategy for survival in the PI-IUGR fetus but with potential maladaptive consequences for reduced nutrient sensing and insulin sensitivity in postnatal life.

The goal of this study is to develop a more comprehensive theoretical understanding of the processes by which people can benefit from mental health consumer-run organizations (CROs). To accomplish this goal, the concept of roles is used to create a preliminary framework that draws connections between several established theoretical explanations. To ground theory development in empirical data, 194 CRO members from 20 CROs answered open-ended questions about what personal changes occurred as a result of their CRO involvement and what CRO participation experiences enabled personal change. Data analysis led to the identification of 18 personal change categories and 7 experiences that led to change. These categories were integrated into the preliminary theoretical framework, which needed to be extended to accommodate all categories. While inevitably tentative, the final conceptualization provides a more comprehensive understanding of the processes by which people can benefit from CRO participation.

In this study, we determined rates of lysine metabolism in fetal sheep during chronic hypoglycemia and following euglycemic recovery and compared results with normal, age-matched euglycemic control fetuses to explain the adaptive response of protein metabolism to low glucose concentrations. Restriction of the maternal glucose supply to the fetus lowered the net rates of fetal (umbilical) glucose (42%) and lactate (36%) uptake, causing compensatory alterations in fetal lysine metabolism. The plasma lysine concentration was 1.9-fold greater in hypoglycemic compared with control fetuses, but the rate of fetal (umbilical) lysine uptake was not different. In the hypoglycemic fetuses, the lysine disposal rate also was higher than in control fetuses due to greater rates of lysine flux back into the placenta and into fetal tissue. The rate of CO2 excretion from lysine decarboxylation was 2.4-fold higher in hypoglycemic than control fetuses, indicating greater rates of lysine oxidative metabolism during chronic hypoglycemia. No differences were detected for rates of fetal protein accretion or synthesis between hypoglycemic and control groups, although there was a significant increase in the rate of protein breakdown (P<0.05) in the hypoglycemic fetuses, indicating small changes in each rate. This was supported by elevated muscle specific ubiquitin ligases and greater concentrations of 4E-BP1. Euglycemic recovery after chronic hypoglycemia normalized all fluxes and actually lowered the rate of lysine decarboxylation compared with control fetuses (P<0.05). These results indicate that chronic hypoglycemia increases net protein breakdown and lysine oxidative metabolism, both of which contribute to slower rates of fetal growth over time. Furthermore, euglycemic correction for 5 days returns lysine fluxes to normal and causes an overcorrection of lysine oxidation.

Technological innovation--broadly defined as the development and introduction of new drugs, devices, and procedures--has played a major role in advancing the field of cardiothoracic surgery. It has generated new forms of care for patients and improved treatment options. Innovation, however, comes at a price. Total national health care expenditures now exceed $2 trillion per year in the United States and all current estimates indicate that this number will continue to rise. As we continue to seek the most innovative medical treatments for cardiovascular disease, the spiraling cost of these technologies comes to the forefront. In this article, we address 3 challenges in managing the health and economic impact of new and emerging technologies in cardiothoracic surgery: (1) challenges associated with the dynamics of technological growth itself; (2) challenges associated with methods of analysis; and (3) the ways in which value judgments and political factors shape the translation of evidence into policy. We conclude by discussing changes in the analytical, financial, and institutional realms that can improve evidence-based decision-making in cardiac surgery.

My previous research led to the development of a theoretical model explaining the processes by which people can benefit from consumer-run organizations (CROs). This study builds on that work by exploring the ability of the conceptual framework to capture the complexity of seven diverse life history narratives from participants at one CRO. To construct life history narratives, I used data from participant observation and a series of in-depth, minimally structured interviews. Application of the proposed conceptual framework to the narratives provides a consistent structure that organizes the experiences of informants into meaningful components. This application of the framework to the data also enables an exploration of the framework's ability to account for the lives of all informants. This analysis leads to conclusions on the conceptual framework's ability to explain how people benefit from CROs.

Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic beta-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 +/- 0.01 Glu vs. 0.10 +/- 0.01 ng/mL Sal) nor beta-cell mass (65.2 +/- 10.3 Glu vs. 74.7 +/- 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 +/- 0.5 Glu vs. 2.7 +/- 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 +/- 0.8 Glu vs. 51.6 +/- 0.8 Sal, p < 0.05) and lactate (7.74 +/- 3.82 Glu vs. 2.47 +/- 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses.

During late gestation, amino acids and insulin promote skeletal muscle protein synthesis. However, the independent effects of amino acids and insulin on the regulation of mRNA translation initiation in the fetus are relatively unknown. The purpose of this study was to determine whether acute amino acid infusion in the late-gestation ovine fetus, with and without a simultaneous increase in fetal insulin concentration, activates translation initiation pathway(s) in skeletal muscle. Fetuses received saline (C), mixed amino acid infusion plus somatostatin infusion to suppress amino acid-stimulated fetal insulin secretion (AA+S), mixed amino acid infusion with concomitant physiological increase in fetal insulin (AA), or high-dose insulin infusion with euglycemia and euaminoacidemia (HI). After a 2-h infusion period, fetal skeletal muscle was harvested under in vivo steady-state conditions and frozen for quantification of proteins both upstream and downstream of mammalian target of rapamycin (mTOR). In the AA group, we found a threefold increase in ribosomal protein S6 kinase (p70(S6k)) and Erk1/2 phosphorylation; however, blocking the physiological rise in insulin with somatostatin in the AA+S group prevented this increase. In the HI group, Akt, Erk1/2, p70(S6k), and ribosomal protein S6 were highly phosphorylated and 4E-binding protein 1 (4E-BP1) associated with eukaryotic initiation factor (eIF)4E decreased by 30%. These data show that insulin is a significant regulator of intermediates involved in translation initiation in ovine fetal skeletal muscle. Furthermore, the effect of amino acids is dependent on a concomitant increase in fetal insulin concentrations, because amino acid infusion upregulates p70(S6k) and Erk only when amino acid-stimulated increase in insulin occurs.

Since the 1950s, people with mental illness and their families have been organizing a wide range of self-directed, mutual support oriented initiatives, including self-help groups, nonprofit organizations, and businesses. These initiatives have become increasingly widespread over the years and today mental health self-help initiatives outnumber traditional mental health organizations in the United States (Goldstrom et al., Admin Policy Mental Health Mental Health Serv Res 33:92-103, 2006). Mental health self-help embodies much of what community psychologists promote, including the self-directed organization of people to create social change and facilitate personal transformation. This special issue provides new insight into several prominent areas of inquiry surrounding these low-cost interventions including: (1) their evidence base; (2) the processes by which people benefit; (3) how they interface with the mental health system; and (4) the value dilemmas they face.

The goal of this study was to examine how different types of participation in a consumer-run organization (CRO) are related to recovery. More specifically, this study uses structural equation modeling to examine the relative impact of empowering and socially supportive participation experiences on progress towards recovery among 250 CRO members from 20 CROs. An empowering participation experience refers to involvement in leadership roles and contribution to organizational functioning. A socially supportive participation experience refers to social involvement in mutually supportive friendships with intimacy and sharing. Results indicate that both types of participation are associated with recovery, although a socially supportive participation experience maintains a stronger relationship with recovery than an empowering participation experience. Findings are consistent with the idea that CROs should encourage both types of participation. Drawing from over ten years of experience supporting CROs, the discussion section explores several strategies CROs can use to foster empowering and socially supportive participation experiences.

Nonglucose carbohydrates such as galactose, mannose, and inositol play a clinically important role in fetal and neonatal nutrition, though little is known about their metabolism in the neonate. The aim of this study was to determine whether postprandial changes in plasma carbohydrate and sugar alcohol concentrations are affected by clinical variables such as postnatal age (PNA), milk type, feeding volume, or feeding duration in term newborns. Neonates (n = 26) taking intermittent enteral feedings were enrolled. Blood samples were obtained at baseline (immediately before the start of a feeding) and at 2-3 subsequent time points up to 110 min. Postprandial rise was only observed for plasma glucose concentrations [Glu] and plasma galactose concentrations [Gal] and clinical variables did not predict this change. Despite equimolar delivery in milk, the median of [Glu] rise minus [Gal] rise from baseline to second postprandial plasma sample was 674 microM (-38, 3333 microM; p < 0.0001), reflecting efficient hepatic first-pass metabolism of galactose. A significant PNA effect on [Gal] was observed such that for each day PNA there was an 18% decrease in [Gal] (p = 0.03). [Gal] are a function of PNA, suggesting maintenance of a significant ductus venosus shunt in term infants.

Consumer-run organizations (CROs) are self-help oriented organizations that are run entirely by consumers (people who use or have used mental health services). The current study utilizes an organizational capacity framework to explore the needs of operating CROs. This framework includes four core capacity areas: (1) technical, (2) management, (3) leadership, and (4) adaptive capacity. An analysis reveals that the greatest organizational needs are related to technical and management capacities. Implications are discussed in terms of strategies and activities that CRO leaders and mental health professionals and administrators can use to strengthen the organizational capacity of CROs in their community.

Rebecca Probert is a Senior Lecturer in Law at the University of Warwick. She specialises in family law and is currently writing a book on the law of marriage in the eighteenth century. Liam D'Arcy Brown is her husband and chief research assistant.

Globalization, migration, and widespread health disparities call for interdisciplinary approaches to improve health care at home and abroad. Health professions students are pursuing study abroad in increasing numbers, and universities are responding with programs to address these needs. The University of Wisconsin (UW)-Madison schools of medicine and public health, nursing, pharmacy, veterinary medicine, and the division of international studies have created an interdisciplinary center for global health (CGH). The CGH provides health professions and graduate students with courses, field experiences, and a new Certificate in Global Health. Educational programs have catalyzed a network of enthusiastic UW global health scholars. Partnerships with colleagues in less economically developed countries provide the foundation for education, research, and service programs. Participants have collaborated to improve the education of health professionals and nutrition in Uganda; explore the interplay between culture, community development, and health in Ecuador; improve animal health and address domestic violence in Mexico; and examine successful public health efforts in Thailand. These programs supply students with opportunities to understand the complex determinants of health and structure of health systems, develop adaptability and cross-cultural communication skills, experience learning and working in interdisciplinary teams, and promote equity and reduce health disparities at home and abroad. Based on the principles of equity, sustainability, and reciprocity, the CGH provides a strong foundation to address global health challenges through networking and collaboration among students, staff, and faculty within the UW and beyond.

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA and phosphorylation of cAMP response element binding protein at Ser(133) were both increased, with no change in Akt, forkhead transcription factor FoxO1, hepatocyte nuclear factor-4alpha, or CCAAT enhancer binding protein-beta. These results demonstrate that chronic fetal hypoglycemia triggers signals that can activate gluconeogenesis in the fetal liver.

Two Ca2+-dependent signaling pathways, mediated by the Ca2+-activated phosphatase calcineurin and by the Ca2+-activated kinase Ca2+/calmodulin-dependent kinase (CaMK), are both believed to function in fast-to-slow skeletal muscle fiber type transformation, but questions about the relative importance of the two pathways still remain. Here, the differential gene expression during fast-to-slow fiber type transformation was studied using cultured adult flexor digitorum brevis (FDB) fibers and a custom minimicroarray system containing 21 fiber type-specific marker genes. After 3 days of culture, unstimulated fibers showed a generally slower gene expression profile; 3 days of electric field stimulation of cultured FDB fibers with a slow fiber-type pattern transformed the fibers to an even slower gene expression profile. Unstimulated FDB fibers overexpressing constitutively active calcineurin featured a slower gene expression profile, except four genes, indicating that transformation occurred, but was incomplete with activation of the calcineurin pathway alone. In both unstimulated FDB fibers and slow-type electrically stimulated FDB fibers, blocking of CaMK pathway with KN93 generated a faster gene expression profile compared with the negative control KN92, indicating that CaMK pathway functions during the transformation induced by both unstimulated culturing and slow fiber-type electrical stimulation. Moreover, neither the calcineurin nor the CaMK pathway alone could maximally activate the transformation, and coordination of the two pathways is required to accomplish a complete fast-to-slow fiber type transformation.

Ca(+) sparks are rare in healthy adult mammalian skeletal muscle but may appear when adult fiber integrity is compromised, and occur in embryonic muscle but decline as the animal develops. Here we used cultured adult mouse flexor digitorum brevis muscle fibers to monitor occurrence of Ca(2+) sparks during maintenance of adult fiber morphology and during eventual fiber morphological dedifferentiation after various times in culture. Fibers cultured for up to 3 days retain normal morphology and striated appearance. Ca(2+) sparks were rare in these fibers. At 5-7 days in culture, many of the original muscle fibers exhibit sprouting and loss of striations, as well as the occurrence of spontaneous Ca(2+) sparks. The average rate of occurrence of Ca(2+) sparks is >10-fold higher after 5-7 days in culture than in days 1-3. With the use of fibers cultured for 7 days, application of the Ca(2+) channel blockers Co(2+) or nifedipine almost completely suppressed the occurrence of Ca(2+) sparks, as previously shown in embryonic fibers, suggesting that Ca(2+) sparks may be generated by similar mechanisms in dedifferentiating cultured adult fibers and in embryonic fibers before final differentiation. The sarcomeric disruption observed under transmitted light microscopy in dedifferentiating fibers was accompanied by morphological changes in the transverse (T) tubular system, as observed by fluorescence confocal imaging of both an extracellular marker dye and membrane staining dyes. Changes in T tubule morphology coincided with the appearance of Ca(2+) sparks, suggesting that Ca(2+) sparks may either be a signal for, or the result of, disruption of DHPR-ryanodine receptor 1 coupling.

This study explores how consumer-run organizations (CROs) can maintain independence while meeting the accountability needs of funding agencies. The importance of both funding agency needs for accountability and CRO needs for independence are discussed. A goal-tracking process is proposed as a potential strategy for balancing the potentially conflicting needs of accountability and independence. To demonstrate the utility of the goal tracking approach, this study analyzes goal tracking documentation in 3 years of quarterly reports from 21 CROs (also known as consumer drop-in centers and self-help agencies). Results detail the different goals of CROs. A 68% goal achievement rate suggests general organizational competence. Furthermore, CRO operations appear to be relatively cost-efficient, with an average of $11.51 spent per person per day. The analysis of quarterly reports leads to a discussion of several insights that may be useful to CROs, funding agencies, researchers, and mental health professionals.

We studied the effect of acute hyperinsulinemia on amino acid (AA) utilization and oxidation rates independent of insulin-enhanced glucose metabolism in fetal sheep. Metabolic studies were conducted in each fetus (n = 11) under three experimental periods. After control period (C) study, a fetal hyperinsulinemic-euglycemic-euaminoacidemic (HI-euG-euAA) clamp was established, followed by a hyperinsulinemic-hypoglycemic-euaminoacidemic (HI-hypoG-euAA) clamp to decrease glucose metabolic rates toward C values. Infusions of (3)H(2)0, L-[1-(13)C]leucine, and [(14)C(U)]glucose were administered to measure blood flow, leucine oxidation, and fetal glucose uptake, utilization, and oxidation in each period. Fetal glucose utilization rate increased 1.7-fold with hyperinsulinemia (C 5.8 +/- 0.8 mg.kg(-1).min(-1), HI-euG-euAA 10 +/- 1.3 mg.kg(-1).min(-1), P < 0.0001), returning to rates not different from C with hypoglycemia (HI-hypoG-euAA 7.1 +/- 0.9 mg.kg(-1).min(-1) vs. C value, P = 0.15). Fetal glucose oxidation rate increased 1.7-fold with hyperinsulinemia (C 3.1 +/- 0.2 mg.kg(-1).min(-1), HI-euG-euAA 5.4 +/- 0.4 mg.kg(-1).min(-1), P < 0.0001) and decreased to near control rates with hypoglycemia (4.0 +/- 0.3 HI-hypoG-euAA vs. C value, P = 0.006). AA utilization rates increased with hyperinsulinemia for all essential and most nonessential AAs (P < 0.001) and did not change when insulin-induced increases in glucose utilization returned to control rates. Leucine oxidation rate increased 1.7-fold with hyperinsulinemia (C 1.0 +/- 0.3 micromol.min(-1).kg(-1), HI-euG-euAA 1.7 +/- 0.3 micromol.min(-1).kg(-1), P < 0.002) and did not change when glucose oxidation rate was decreased with hypoglycemia. These results demonstrate that, in fetal sheep, insulin promotes AA utilization and oxidation independent of its simultaneous effects on glucose metabolism. In acute hyperinsulinemic conditions, AA oxidation does not change when insulin-induced glucose utilization is prevented.

Bright ideas for health reform abound in Western nations, but moving proposals into policy requires surmounting political challenges. This paper briefly reviews three central challenges: installing reforms not merely "on the public agenda," but also high on the agendas of public and private stakeholders; designing for the reformed system a division of labour acceptable to key actors and institutions; and finding a reform model that is both substantively plausible and politically appealing. Successful hurdling of these challenges is easier said than done.

In this paper, the problem of interest is efficient estimation of log-normal means. Several existing estimators are reviewed first, including the sample mean, the maximum likelihood estimator, the uniformly minimum variance unbiased estimator and a conditional minimal mean squared error estimator. A new estimator is then proposed, and we show that it improves over the existing estimators in terms of squared error risk. The improvement is more significant with small sample sizes and large coefficient of variations, which is common in clinical pharmacokinetic (PK) studies. In addition, the new estimator is very easy to implement, and provides us with a simple alternative to summarize PK data, which are usually modelled by log-normal distributions. We also propose a parametric bootstrap confidence interval for log-normal means around the new estimator and illustrate its nice coverage property with a simulation study. Our estimator is compared with the existing ones via theoretical calculations and applications to real PK studies., (Copyright 2005 John Wiley & Sons, Ltd.)

The purpose of this 2-week, double-blinded, controlled clinical trial was to evaluate the efficacy of topical amino acid-complexed zinc gluconate formulated with boric acid (ZGB) or acetic acid (ZGA) versus a topical placebo in the treatment of yeast otitis externa in dogs. Included in the study were dogs with otitis externa and a cytopathological finding of yeast organisms in the affected ear. Ears were treated with the placebo, ZGA, or ZGB medications. Yeast counts as well as clinical appearance of the ears were monitored. Results revealed that ZGB significantly reduced the number of yeast organisms in cases of otitis externa.

The recent decline, indeed perhaps dismantling, of managed care is sometimes treated as both consequence and cause of the political reempowerment of medical providers, whose professional dominance managed care had challenged. Drawing evidence from Round III of the Community Tracking Study of the Center for Studying Health System Change, this article reviews the politics of four "arenas" of managed care regulation--prompt payment, mandated benefits, external appeals, and financial solvency--and concludes that the power of providers is contingent on patterns of coalition and conflict that differ across the discrete arenas. The zero-sum connotations of the "de" and "re" empowerment of providers under managed care fail to capture the subtlety of providers' search for fresh cultural, economic, and political resources in shifting policy contexts.

Two types of Barbarea vulgaris var. arcuata, the G-type and the P-type, differed in resistance to larvae of the diamondback moth (DBM) Platella xylostella. Rosette plants of the G-type were fully resistant to the DBM when grown in a greenhouse or collected in the summer season, but leaves collected during the late fall were less resistant, as previously found for flea beetle resistance. The P-type was always susceptible. Extracts of resistant leaflets inhibited larval growth in a bioassay, and a growth-inhibiting fraction was isolated by activity-guided fractionation. A triterpenoid saponin (1) was isolated from this fraction and identified as 3-O-beta-cellobiosyloleanolic acid from spectroscopic data and analysis of hydrolysis products. The decrease in resistance of the G-type in the fall was correlated with a decrease in the level of 1, from 0.6-0.9 to < 0.2 micromol/g dry wt. Compound 1 was not detected in the susceptible P-type. We conclude that 1 is correlated with the variable resistance of B. vulgaris foliage to the DBM.

Advocates of U.S. national health insurance tend to share an image that highlights universal standards of coverage, social insurance financing, and national administration--in short, the basic features of Medicare. Such an approach is said to be good (equitable and efficient) policy and equally good politics. Medicaid, by contrast, is often taken to exemplify poor policy and poorer politics: means-tested eligibility, general revenue financing, and federal/state administration, which encourage inequities and disparities of care. This stark juxtaposition fails, however, to address important counterintuitive elements in the political evolution of these programs. Medicare's benefits and beneficiaries have stayed disturbingly stable, but Medicaid's relatively broad benefits have held firm, and its categories of beneficiaries have expanded. Repeated alarms about "bankruptcy" have undermined confidence in Medicare's trust funding, while Medicaid's claims on the taxpayer's dollar have worn well. Medicare's national administration has avoided disparities, but at the price of sacrificing state and local flexibility that can ease such "reforms" as the introduction of managed care. That Medicaid has fared better than a "poor people's program" supposedly could has provocative implications for health reform debates.

The Rekindling Reform initiative examined the health systems of 4 countries: Canada, France, Germany, and Great Britain (United Kingdom). From the 4 country reports published in this issue of the American Journal of Public Health, 10 crosscutting themes emerge: (1) coverage, (2) funding, (3) costs, (4) providers, (5) integration, (6) markets, (7) analysis, (8) supply, (9) satisfaction, and (10) leadership. Lessons for the United States are presented under each point.

This article provides new empirical data about the viability and the care management activities of Medicaid managed-care plans sponsored by provider organizations that serve Medicaid and other low-income populations. Using survey and case study methods, we studied these "safety-net" health plans in 1998 and 2000. Although the number of safety-net plans declined over this period, the surviving plans were larger and enjoying greater financial success than the plans we surveyed in 1998. We also found that, based on a partnership with providers, safety-net plans are moving toward more sophisticated efforts to manage the care of their enrollees. Our study suggests that, with supportive state policies, safety-net plans are capable of remaining viable. Contracting with safety-net plans may not be an efficient mechanism for enabling Medicaid recipients to "enter the mainstream of American health care," but it may provide states with an effective way to manage and coordinate the care of Medicaid recipients, while helping to maintain the health care safety-net for the uninsured.

Health plans formed by safety-net providers serve large numbers of Medicaid beneficiaries. Through a series of case studies, we examined the care management tools used by leading safety-net plans. These plans do not rely on the coercive, command-style tools of managed care. They rely instead on tools that emphasize partnership with providers: sharing data about practice patterns, using provider profiles and financial bonuses to encourage particular practice patterns, and developing disease management programs that encourage patient compliance with treatment decisions that the plans make little effort to shape. The evidence suggests that these are promising practices but that even these leaders still have a long way to go.

Adult skeletal muscle fibers can be isolated and cultured but tend to dedifferentiate and sprout with time in culture. We examined isolated adult mouse flexor digitorum brevis muscle fibers under various culture conditions by monitoring maintenance of the same fibers at 2-d intervals using survival analysis. Fibers plated on laminin and cultured in serum-free media did not show sprouting and exhibited significantly (P < 0.0001) longer survival (median survival time, T(50) = 10.2 d) than fibers in serum-containing media (T(50) = 3.3 d). Cell proliferation was markedly suppressed in serum-free cultures. Multiple or delayed Ca(2+) transients in response to brief field stimulation were often observed in dedifferentiated fibers after several d in serum-containing media but were not observed in fibers in serum-free media. The addition of cytosine arabinoside to serum-containing cultures did not prolong fiber survival (P = 0.39) and did not eliminate sprouting but did greatly suppress proliferation of nonmuscle cells. Fibers cultured in agarose gel with serum exhibited small, bud-like extensions but no sprouts and did not survive as long (T(50) = 6.2 d) as fibers plated on laminin and cultured in serum-free media (T(50) = 10.2 d) did. These results demonstrate that both morphological and physiological properties of fibers become modified in serum-containing media but can be retained by culturing without serum.

The in situ distribution of the alpha and beta myosin light chains was investigated at the subsarcomeric and subfilament levels in individual fibers of the superficial flexor muscle (SFM) of the lobster, Homarus americanus. Polyclonal antibodies were produced against the two classes of myosin light chains and used for subsequent immunolocalization on thin sections of sarcomeres and on isolated filaments from both the medial and lateral fiber bundles of the SFM. The beta myosin light chains were uniformly distributed within the crossbridge region of sarcomeres of both medial and lateral bundles. The alpha myosin light chains were uniformly distributed within the crossbridge region of sarcomeres from the medial bundle, but were nonuniformly distributed over the crossbridge region of lateral bundle sarcomeres. In the latter, the number of alpha myosin light chains was highest toward the center of the thick filaments, diminishing towards the ends. Similar distributions of alpha light chains were found in isolated myosin filaments. These data demonstrate that heterogeneity in protein composition extends to the level of the myosin filament and suggest that the myosin filament substructure in lobster may be different than that found in vertebrate skeletal muscle., (Copyright 2001 Wiley-Liss, Inc.)

Throughout the 1990s states sought politically acceptable policies to reduce the ranks of the uninsured. Visions of comprehensive health reform and universal coverage yielded by mid-decade to more modest measures to repair private health insurance markets, and to these enactments were added several new public programs (state and federal) to expand coverage for lower-income children and, in some cases, adults. Because governments remain ill equipped to counter the power of business, insurers, and providers in conflicts fought on private turf, reform agendas have been more readily set, moved, and cleared in public-sector arenas. Although the number of uninsured rose steadily until 1999, "catalytic federalism"--the accelerating interplay between state and federal reform forces and funds--may be putting the programmatic foundations for broader coverage incrementally into place.

Objective: To evaluate the impact of interpersonal communication (IPC) training on practice and patient satisfaction and to determine the acceptability of this training to providers in a developing country., Design: The study used a pre-post design with treatment and control groups. Data collection methods included interaction analysis of audio-taped clinical encounters, patient exit interviews, and a self-administered questionnaire for health providers., Study Participants: Interaction analysis was based on an experimental group of 24 doctors and a control group of eight with multiple observations for each provider). Exit interviews were carried out with 220 pre-test patients and 218 post-test patients. All 87 health providers who received training responded to the self-administered questionnaire., Intervention: A brief in-service training programme on interpersonal communications was presented in three half-day sessions; these focused on overall socio-emotional communication, problem solving skills and counselling., Main Outcome Measures and Results: The IPC intervention was associated with more communication by trained providers (mean scores of 136.6 versus 94.4; P = 0.001), more positive talk (15.93 versus 7.99; P = 0.001), less negative talk (0.11 versus 0.59; P = 0.018), more emotional talk (15.7 versus 5.5; P = 0.021), and more medical counselling (17.3 versus 11.3; P = 0.026). Patients responded by communicating more (mean scores of 113.8 versus 79.6; P = 0.011) and disclosing more medical information (54.7 versus 41.7; P = 0.002). Patient satisfaction ratings were higher for providers who had received the training and providers reported training to be relevant and useful., Conclusions: Further validation of IPC skills and simplification of assessment methods are needed if IPC is to be an area for routine monitoring and quality improvement.

Health care providers that have traditionally served the poor are forming their own managed care plans, often in alliance with local safety-net peers. These alliances make it easier to raise needed capital, increase the pool of likely enrollees, and enable plans to benefit from efficiencies of scale. At the same time, however, the alliances often are undermined by conflicts of interest among the different sponsors and between the sponsors and the plan. This paper suggests that these plans are most likely to do well when the state makes special efforts to help and when plans have the leadership and financial reserves to take advantage of their supportive state policies.

Despite extensive knowledge of many muscle A-band proteins (myosin molecules, titin, C-protein (MyBP-C)), details of the organization of these molecules to form myosin filaments remain unclear. Recently the myosin head (crossbridge) configuration in a relaxed vertebrate muscle was determined from low-angle X-ray diffraction (Hudson et al. (1997), J Mol Biol 273: 440-455). This showed that, even without C-protein, the myosin head array displays a characteristic polar pattern with every third 143 A-spaced crossbridge level particularly prominent. However, X-ray diffraction cannot determine the polarity of the crossbridge array relative to the neighbouring actin filaments; information crucial to a proper understanding of the contractile event. Here, electron micrographs of negatively-stained goldfish A-segments and of fast-frozen, freeze-fractured plaice A-bands have been used to determine the resting myosin head polarity relative to the M-band. In agreement with the X-ray data, the prominent 429 A-spaced striations are seen outside the C-zone, where no non-myosin proteins apart from titin are thought to be located. The head orientation is with the concave side of the curved myosin heads (containing the entrance to the ATP-binding site) facing towards the M-band and the convex surface (containing the actin-binding region at one end) facing away from the M-band.

Across the nation, public officials are encouraging or requiring Medicaid beneficiaries to enroll in managed care. In this article, we report on a study of the implementation of Medicaid managed care in New York City. Several findings are clear. First, government officials need to treat health plans as partners rather than adversaries; in New York, the relationship between the state and the plans is far too adversarial. Second, effective managed care requires good management information systems; New York officials are collecting an enormous amount of data but not much useful information. Third, effective implementation of Medicaid managed care is slow going; New York's effort to dramatically accelerate the enrollment process did not work.

Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome.

Purpose: We herein report updated survival and toxicity data on the entire cohort of 53 eligible patients treated on North Central Cancer Treatment Group (NCCTG) protocol 86-72-52, which is now closed., Methods and Materials: An initial report was published in this journal in 1995. No substantive changes in the conclusions of that report were identified in this analysis. Median survival was 9.6 months for the entire cohort; median survival for the 20 patients who completed the prescribed protocol treatment was 20.7 months. The hematologic and non-hematologic toxicity distributions are virtually the same as those reported in the original paper., Results: Results are given for the entire group and for subsets defined by age < or = 60 versus > 60 years, and < 70 versus > or = 70 years of age., Conclusions: No significant differences were observed in any of the outcome variables by age group. There was, however, a nonsignificant suggestion of poorer outcome in those who were > 60 years of age.

Nearly every state is encouraging or requiring Medicaid beneficiaries to enroll in managed care delivery systems. In New York City, Medicaid officials began with an incremental, but not insignificant, managed care initiative. Buoyed by its success, New York policy makers tried, and failed, to accelerate the transition to managed care. The legacy of that failure still plagues them. A comparison of such initiatives in other states indicates that most state officials have remembered what New York's leaders temporarily forgot, namely, that Medicaid managed care is a complex exercise that demands consultation and consensus building.