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PubMed2003

Evaluating citizen advisory boards: the importance of theory and participant-based criteria and practical implications.

The role of risk communication and public participation in environmental and public policy decision making has significantly increased over the last 15 years and remains an important social policy issue. In spite of this emphasis, government officials and participants in the process continue to struggle with what makes for "good" public participation. This study used two frameworks--one theoretical and one participant-based-to evaluate two U.S Army Restoration Advisory Boards (RABs). The theoretical framework explores the extent to which the RABs facilitate Habermas's idealized conditions of speech as related to fairness. Not surprisingly, we found that the two RABs do not consistently foster the idealized aspects of fairness suggested by Habermas. The participant-based criteria were elicited through interviews with participants from the various stakeholder groups represented on the RAB, direct observation of RAB meetings, and a review of RAB-related documents. We found that participants' value outcomes (the results of participatory processes) and not just the process itself, which is the focus of the theoretical framework. We also found that participants in the various stakeholder groups had different perceptions of the goals of the participatory process, which were closely related to their notions of success. Our results illustrate both the complexity and importance of using multiple frameworks for evaluating participatory efforts and the need for more systematic evaluation.

Journal Article↗
PubMed2003

Evaluating risk communication about fish consumption advisories: efficacy of a brochure versus a classroom lesson in Spanish and English.

Presentation format can influence the way target audiences understand risk-related information. Brochures or fish fact sheets are the methods traditionally used by state agencies to inform the public about fish consumption advisories and the risks from consuming fish. This study examines the efficacy of presenting information about the risks from consuming contaminated fish and shellfish in two different formats: a brochure and classroom presentation. The two instruments were developed and tested in Spanish and English, reflecting the local ethnic composition in the Newark Bay Complex. The instruments were tested on women of child-bearing age at the Women, Infants, and Children Center in Elizabeth, New Jersey. Detailed diagrams were used in both presentations, including contaminated fish species, fish preparation methods, and food chain bioaccumulation and transmission to the fetus. There were few language-related differences in the efficacy of the classroom lesson, and the main ideas were understood by both groups. Where there were significant differences in understanding about the risks from consuming fish or crabs from the contaminated waters of Newark Bay, in all cases the women exposed to the classroom lesson had a better understanding than those who read the brochure. Ninety-six percent of the women who heard the lesson understood that it was unsafe to eat fish from the port, compared to 72% of those reading the brochure. Both formats succeeded in imparting information to most women about the area under advisories, the fish species under advisories, and transmission of toxins to the fetus. Information on fish preparation was recalled less clearly, partly because women were asked to relate methods to reduce the risk from consuming fish from 11 presented, and most recalled only two or three of the list. The advantages and disadvantages of conducting short classes to women of child-bearing age are discussed.

Adult↗
PubMed2003

Communicating worst-case scenarios: neighbors' views of industrial accident management.

The prospect of industrial accidents motivated the U.S. Congress to require in the Clean Air Act of 1990 that manufacturing facilities develop Risk Management Plans (RMP) to submit to the U.S. Environmental Protection Agency (USEPA) by July 1999. Industry worried that the requirement to communicate to the public a "worst-case scenario" would arouse unnecessary and counterproductive fears among industry neighbors. We report here the results of focus groups and surveys with such neighbors, focusing particularly upon their reactions to messages about a hypothetical worst-case scenario and management of these risks by industry, government, and other parties. Our findings confirmed our hypotheses that citizens would be skeptical of the competence and trustworthiness of these managers and that this stance would color their views of industrial-facility accident risks. People with job ties to industry or who saw industrial benefits to the community as exceeding its risks had more positive views of industrial risks, but still expressed great concern about the risk and doubt about accident management. Notwithstanding these reactions, overall respondents welcomed this and other related information, which they wanted their local industries to supply. Respondents were not more reassured by additional text describing management of accidents by government and industry. However, respondents did react very positively to the concept of community oversight to review plant safety. Claims about the firm's moral obligation or financial self-interest in preventing accidents were also received positively. Further research on innovative communication and management of accident risks is warranted by these results, even before recent terrorist attacks made this topic more salient.

Accidents, Occupational↗
PubMed2003

How reassuring are risk comparisons to pollution standards and emission limits?

Pollutant emissions or ambient levels are often justified by reference to a higher benchmark, such as a public health standard or permit limit. However, does this risk comparison persuade the public audiences to whom it is frequently directed that such pollution levels are "acceptable"? A substantial proportion of people living within one mile of New Jersey's industrial facilities, perhaps as much as half, is indeed reassured by a comparison to such benchmarks. Positive attitudes toward discharge limits were linked to speaking English at home; positive attitudes toward drinking water standards were associated with seeing local benefits of industry as outweighing its risks, not speaking English, and relative youth (49 years old or less). Three scenarios involving drinking water contamination varied pre- and post-treatment levels of the pollutant, though all post-treatment levels were below the standard. In all cases great concern was expressed, with no significant differences across scenarios; net benefits, being white, and non-English speaking were linked to lower concern. Relative trust seems a better explanation of different attitudes toward benchmark comparisons than varying levels of knowledge, but both hypotheses have drawbacks that merit further testing. These results imply that people with negative views of industry or government, the ones officials might most wish to reassure, will tend to doubt that regulatory benchmarks offer a valid risk comparison.

Adult↗
PubMed2005

Pharmacy utilization and the Medicare Modernization Act.

To control expenditures and use medications appropriately, the Medicare drug coverage program has established pharmacy utilization management (PUM) measures. This article assesses the effects of these strategies on the care of seniors. The literature suggests that although caps on drug benefits lower pharmaceutical costs, they may also increase the use of other health care services and hurt health outcomes. Our review raises concerns regarding the potential unintended effects of the Medicare drug program's PUM policies for beneficiaries. Therefore, the economic and clinical impact of PUM measures on seniors should be studied further to help policymakers design better drug benefit plans.

Aged↗
PubMed1996

In vitro contractility of stimulated and non-stimulated human gallbladder muscle.

In an attempt to define, more clearly, the nature of gallbladder contraction we obtained muscle strips from human gallbladder wall, removed at cholecystectomy. Samples were taken from various areas of the gallbladder to seek evidence of a dominant axis of contraction. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8) and carbachol, and, to determine maximal contractile force, 0.25 M potassium chloride. No differences were seen between samples taken from the long-itudinal, circular and oblique axes. In a second series of experiments, samples were taken from the body and neck regions of the gallbladder. In these, it was seen that the samples from the body contracted more forcefully than those of the neck tissue and that they were more sensitive to carbachol stimulation. The difference in response to CCK-8 measured in the strips from the body and cystic duct/neck of the gallbladder cannot be explained by a difference in sensitivity to CCK-8, but is mainly due to the difference in the amount of muscle tissue present. Strips from the body are more sensitive to muscarinic stimulation that those from the neck. Overall, there is a functional difference in sensitivity between the body and neck which would serve to facilitate bile flow into the common bile duct during gallbladder contraction.

Carbachol↗
PubMed2004

The study of mitoxantrone as a potential immunosuppressor in transgenic pig renal xenotransplantation in baboons: comparison with cyclophosphamide.

Mounting evidence suggests that delayed xenograft rejection (DXR) of discordant xenografts has a strong humoral component. To explore the possibility of targeting this humoral response more efficiently, we performed a preliminary study in baboons immunized against pig blood cells using the immunosuppressor mitoxantrone (Mx). The results from this study showed that, in comparison with cyclophosphamide (CyP), Mx induced a long-lasting depletion of circulating B cells within 6 days of its administration and delayed secondary anti-Gal antibody (Ab) responses to pig blood cell immunizations. Given these results, we next evaluated Mx in an in vivo model of pig to baboon renal xenotransplantation. We performed a series of renal xenotransplantations in baboons using human CD55-CD59 transgenic donor pigs. In the first group of baboons (Mx group; n = 4) Mx was administered 6 days prior to the day of transplantation, the objective being to perform the xenotransplantation in a context where the recipient would have few remaining circulating B cells and thus have an impaired capacity to mount an Ab response to the xenograft. We compared this group to a second group of baboons treated with CyP starting 1 day prior to transplantation (CyP group; n = 2). All baboons receiving Mx or CyP received an additional immunosuppression of cyclosporin A, mycophenolate mofetil and steroids. No hyperacute rejection was observed in either group but all xenografts underwent DXR. Mx did not show superiority to CyP in terms of graft survival with a mean survival time of 8 +/- 2 days compared with 9 days for both CyP-treated baboons. Neither CyP nor Mx decreased serum levels of pre-existing anti-Gal Abs but levels of these Abs decreased dramatically within 1 day of transplantation, likely reflecting their immediate trapping within the xenograft. Interestingly however, in contrast to CyP, Mx inhibited the return of anti-Gal immunoglobulin M (IgM) to the circulation, even at the time of rejection. Nevertheless, strong intragraft deposits of IgM, IgG and the activated complement complex C5b-9 were observed in biopsies at rejection. Furthermore, despite the expected profound depletion of circulating B cells by Mx within 6 days of its administration, biopsies from both groups at rejection displayed a mild B cell infiltrate accompanied by a strong macrophage and intermediate T-cell infiltration, the latter tending to be more abundant in Mx-treated animals. Our data show that in this particular model of pig to baboon xenotransplantation and at the dose used, Mx was not superior to CyP in conferring protection against rejection, despite its capacity to profoundly deplete circulating B cells and to inhibit anti-Gal Ab responses to xenografts. DXR was thus possible without the return of anti-Gal Abs and may have been mediated by the early fixation of pre-existing Abs with secondary complement activation. However, although Mx was not more efficient than CyP in controlling DXR, its capacity to deplete B cells and delay Ab recovery may be beneficial in the context of Gal knockout organ transplantation where the induced Ab response is likely to take precedence over the preformed response.

Animals↗
PubMed2006

Is clinical tolerance realistic in the next decade?

Tolerance to allografts would mean a better quality of life and prognosis for transplant patients. Despite the first descriptions of tolerance to alloantigens over 50 years ago, deliberately induced tolerance in the clinic on a wide scale remains a goal that is not quite in reach. However, much progress has been made in understanding tolerance in rodent models and in the few reports of induced or spontaneously occurring tolerance in humans. Here, we review this progress made in the quest to achieve clinical tolerance.

Animals↗
PubMed2005

High-fat diet prevents cardiac hypertrophy and improves contractile function in the hypertensive dahl salt-sensitive rat.

1. The role that dietary lipid and plasma fatty acid concentration play in the development of cardiac hypertrophy in response to hypertension is not clear. 2. In the present study, we treated Dahl salt-sensitive rats with either normal chow (NC), normal chow with salt added (NC + salt) or a diet high in long-chain saturated fatty acids with added salt (HFD + salt). Cardiac function was assessed by echocardiography and left ventricular (LV) catheterization. 3. The HFD + salt group had significantly higher plasma free fatty acid concentrations and myocardial triglyceride content compared with the NC + salt group, but did not upregulate the activity of the fatty acid oxidation enzyme medium chain acyl-coenzyme A dehydrogenase. Systolic blood pressure was elevated to a similar extent in the NC + salt and HFD + salt groups compared with the NC group. Although LV mass was increased in the NC + salt group compared with the NC group, LV mass in the HFD + salt group did not differ from that of the NC group and was significantly lower than that in the NC + salt group. 4. There was no evidence of cardiac dysfunction in the NC + salt group compared with the NC group; however, high fat feeding significantly increased LV contractile performance (e.g. increased cardiac output and peak dP/dt). 5. In conclusion, the HFD + salt diet prevented the hypertrophic response to hypertension and improved the contractile performance of the heart. It remains to be determined whether preventing cardiac hypertrophic adaptations would be deleterious to the heart if the hypertensive stress is maintained long term.

Animals↗
PubMed2004

Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle.

OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 mumol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pKB values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

Adult↗
PubMed1990

Whether phenylephrine exerts inotropic effects through alpha- or beta-adrenoceptors depends upon the relative receptor populations.

Phenylephrine produced concentration-related positive inotropic responses in isolated left atria and papillary muscles of guinea-pigs and rats. In rat tissues, these responses were unaffected by propranolol but antagonized by prazosin and therefore mediated via alpha 1-adrenoceptors. The alpha 1-adrenoceptor agonist methoxamine also exerted positive inotropic effects in these rat tissues. The maximum alpha-adrenoceptor-mediated effect of methoxamine (relative to the isoprenaline maximum) was greater than that of phenylephrine in left atria (in the presence of propranolol), whereas in papillary muscles phenylephrine exerted the greater maximum. In guinea-pig papillary muscles, the response to phenylephrine was unaffected by prazosin but was antagonized by propranolol and therefore caused by stimulation of beta-adrenoceptors. Methoxamine had no effect in guinea-pig papillary muscles. Guinea-pig left atria produced biphasic concentration-response curves for phenylephrine, the lower portion being antagonized by phentolamine and was therefore alpha-adrenoceptor-mediated, while the upper portion was antagonized by propranolol and therefore beta-adrenoceptor-mediated. Methoxamine exerted a small inotropic response, the maximum of which was similar to that of the first component of the phenylephrine response. Phenylephrine was a partial agonist for the cardiac beta-adrenoceptor. The density of rat ventricular alpha-adrenoceptors was 4 times greater than beta-adrenoceptor density, as measured by [3H]-prazosin and [3H]-dihydroalprenolol binding. This explains why the responses of rat papillary muscles were alpha-adrenoceptor-mediated. In contrast, the density of beta-adrenoceptor binding sites in guinea-pig ventricles was 6 times greater than the alpha-adrenoceptor density. This explains why the phenylephrine responses were beta-adrenoceptor-mediated in guinea-pig papillary muscles. In the left atria of guinea-pigs, which displayed both alpha- and beta-adrenoceptor-mediated responses, the densities of alpha- and beta-adrenoceptor binding sites were similar. Thus, phenylephrine exerts positive inotropic effects through alpha- or beta-adrenoceptors depending upon their relative densities.

Animals↗
PubMed1985

The use of forskolin to investigate the site of cardiac beta-adrenoreceptor supersensitivity.

The positive inotropic responses of left atria and papillary muscles and the positive chronotropic responses of right atria of guinea-pigs to isoprenaline and forskolin were examined. An increase in sensitivity of the three preparations to isoprenaline was observed by lowering the bath temperature from 38 to 30 degrees C as demonstrated by a leftwards shift of the concentration-response curves. A similar degree of supersensitivity was observed for forskolin. Since forskolin is reputed to stimulate adenylate cyclase directly, whereas isoprenaline stimulates via the regulatory nucleotide Ns protein, this would suggest a common site for the supersensitivity at adenylate cyclase. However, the possibility that forskolin also stimulates via the Ns protein in producing cardiac stimulation and that this is the site of hypothermia-induced supersensitivity is discussed. Supersensitivity to isoprenaline was also observed in left atria and papillary muscles from guinea-pigs chronically pretreated with reserpine for 3 days (5 mg/kg at 72 h, 3 mg/kg at 48 and 24 h) or 7 days (0.1 mg/kg daily). In the same tissues, there was no change in the sensitivity to forskolin. The site of the supersensitivity can therefore be concluded to occur before the level of adenylate cyclase activation either directly or via the regulatory Ns protein; possibly at the beta-adrenoreceptor itself.

Animals↗
PubMed1991

Alpha-adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline.

1. The chronotropic and inotropic responses of the young chick heart to noradrenaline have been investigated in isolated right atria, left atria and ventricular strips from 14-day-old chicks. 2. In the presence of desipramine and metanephrine to inhibit amine uptake, concentration-response curves to noradrenaline in all three tissues were shifted to the right by propranolol (1 microM) but were not altered by the presence of either phentolamine (5 microM) or prazosin (10 microM). 3. Similar results were obtained in the presence of cocaine (10 microM) and corticosterone (10 microM) to inhibit amine uptake. Propranolol (0.3-3.0 microM) produced rightward shifts of noradrenaline concentration-response curves which gave pA2 values of 8.1-8.4. Phentolamine (5 microM), in contrast, did not affect responses to noradrenaline in any tissue, either in the absence or presence of propranolol (1 microM). 4. Isoprenaline produced positive chronotropic responses in right atria and positive inotropic responses in left atria and ventricular strips. Methoxamine elicited positive inotropic responses in left atria but only negative chronotropic responses in right atria and negative inotropic responses in ventricular strips. 5. These results demonstrate that cardiac responses to noradrenaline in the chick heart are mediated via beta-adrenoceptors only, and that cardiac alpha-adrenoceptors are not involved in these responses.

Animals↗
PubMed1992

Transient elevation of cardiac beta-adrenoceptor responsiveness and receptor number in the streptozotocin-diabetic rat.

1. The effects on cardiac responsiveness of diabetes of up to 12 weeks duration has been examined in streptozotocin-pretreated rats. 2. Two weeks of diabetes resulted in a supersensitivity of isolated left atria and papillary muscles to isoprenaline, which was associated with an increase in the density of ventricular [3H]-dihydroalprenolol binding sites. 3. The beta-adrenoceptor supersensitivity was still evident in both tissues after 4 weeks of diabetes, but in left atria the supersensitivity was reduced compared with that observed at 2 weeks, while for papillary muscles it was greater than at 2 weeks. 4. Following 12 weeks of diabetes, responses of papillary muscles to isoprenaline were similar to controls, while beta-mediated responses of left atria were significantly depressed. 5. The alpha-adrenoceptor-mediated responses of cardiac tissues to phenylephrine were similar to controls following diabetes of 2 or 4 weeks duration. At 12 weeks, however, papillary muscle alpha-adrenoceptor-mediated responses were enhanced. The change in ventricular responsiveness to phenylephrine was not accompanied by any change in [3H]-prazosin binding to ventricular membranes. 6. The results demonstrate a transient elevation of cardiac beta-adrenoceptor sensitivity and receptor density during acute diabetes and illustrate the time- and tissue-dependence of diabetes-induced changes in cardiac adrenoceptor sensitivity.

Animals↗
PubMed1994

Differential regulation of cardiac alpha- and beta-adrenoceptors by the sympathetic nervous system.

1. The effects of depressed sympathetic function on the inotropic responses of the heart to sympathomimetic amines have been examined in rats immunized against nerve growth factor (NGF) 6 weeks prior to the isolation of cardiac tissues. 2. The activity of tyrosine hydroxylase in cervical sympathetic ganglia and the levels of noradrenaline in ventricular tissue were significantly reduced in NGF-immunized rats. 3. Left atria and papillary muscles from NGF-immunized rats were supersensitive to the beta-adrenoceptor agonist isoprenaline when compared with controls. 4. The responses of cardiac tissues to the alpha-adrenoceptor agonist phenylephrine were unaffected by immunization. 5. These results support the hypothesis that cardiac beta- but not alpha-adrenoceptor sensitivity is regulated by the sympathetic nervous system.

Animals↗