Publications

Genotyping methods for Plasmodium falciparum drug efficacy trials have not been standardized and may fail to accurately distinguish recrudescence from new infection, especially in high transmission areas where polyclonal infections are common. We developed a simple method for genotyping using previously identified microsatellites and capillary electrophoresis, validated this method using mixtures of laboratory clones, and applied the method to field samples. Two microsatellite markers produced accurate results for single-clone but not polyclonal samples. Four other microsatellite markers were as sensitive as, and more specific than, commonly used genotyping techniques based on merozoite surface proteins 1 and 2. When applied to samples from 15 patients in Burkina Faso with recurrent parasitemia after treatment with sulphadoxine-pyrimethamine, the addition of these four microsatellite markers to msp1 and msp2 genotyping resulted in a reclassification of outcomes that strengthened the association between dhfr 59R, an anti-folate resistance mutation, and recrudescence (P = 0.31 versus P = 0.03). Four microsatellite markers performed well on polyclonal samples and may provide a valuable addition to genotyping for clinical drug efficacy studies in high transmission areas.

OBJECTIVE

Alpha and gamma-melanocyte stimulating hormones (MSH) are peptides that possess potent hypertensinogenic actions when injected intravenously or intracerebroventricularly. We sought to define the central receptor(s) mediating these cardiovascular actions.

METHODS

We gave bolus injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 receptor (Mc4r-/-).

RESULTS

Gamma-MSH injected intravenously increased mean arterial pressure (MAP) and heart rate (HR) dose-dependently, with the effect being evident at 10 mol/kg; the maximum increase, at 10 mol/kg, was 38 mmHg in both strains from similar control MAP. Parallel increases in HR also occurred. Injection of the sodium channel blocker, benzamil, 4 microg/kg intracerebroventricularly, before intravenous gamma-MSH completely prevented the increases in MAP and HR in both strains. Injection of 2 x 10 mol/g body weight alpha-MSH intravenously had no effect on MAP or HR in Mc4r wild-type or -/- mice. However, the same dose given intracerebroventricularly to wild-type mice increased MAP from 76 +/- 4 to 95 +/- 5 mmHg at 10 min (P < 0.01) and HR from 416 +/- 15 to 480 +/- 15 beats/min (P < 0.01). In Mc4r-/- mice, the intracerebroventricular administration of the peptide did not alter these variables, in contrast to the results in wild-type mice.

CONCLUSION

Both MSH peptides exert their hypertensinogenic effects through central sites of action, which probably reflect the activation of sympathetic outflow. The actions of intracerebroventricular alpha-MSH appear to be mediated via Mc4r, whereas those of gamma-MSH are independent of its receptor Mc3r, but reflect the activation of a sodium channel in the central nervous system. These results help to reconcile the hypertensive action of gamma-MSH injections with the hypertension observed in states of gamma-MSH deficiency.

Increased lung vascular permeability is an important contributor to respiratory failure in acute lung injury (ALI). We found that a function-blocking antibody against the integrin alphavbeta5 prevented development of lung vascular permeability in two different models of ALI: ischemia-reperfusion in rats (mediated by vascular endothelial growth factor [VEGF]) and ventilation-induced lung injury (VILI) in mice (mediated, at least in part, by transforming growth factor-beta [TGF-beta]). Knockout mice homozygous for a null mutation of the integrin beta5 subunit were also protected from lung vascular permeability in VILI. In pulmonary endothelial cells, both the genetic absence and blocking of alphavbeta5 prevented increases in monolayer permeability induced by VEGF, TGF-beta, and thrombin. Furthermore, actin stress fiber formation induced by each of these agonists was attenuated by blocking alphavbeta5, suggesting that alphavbeta5 regulates induced pulmonary endothelial permeability by facilitating interactions with the actin cytoskeleton. These results identify integrin alphavbeta5 as a central regulator of increased pulmonary vascular permeability and a potentially attractive therapeutic target in ALI.

OBJECTIVES

To assess the effect of functional impairment on family expectations of death and to examine how this association varies by race.

DESIGN

Cross-sectional.

SETTING

Community based.

PARTICIPANTS

Two thousand two hundred thirty-seven family members of decedents from the Health and Retirement Survey (HRS), a national study of persons aged 50 and older.

MEASUREMENTS

Families were interviewed within 2 years of the HRS participant's death. The primary outcome was whether death was expected. The primary predictors were the decedent's functional status (impairment in any activity of daily living (ADL; eating, dressing, transferring, toileting, or bathing) during the last 3 months of life and the decedent's race.

RESULTS

Overall, 58% of families reported that their family member's death was expected. Expecting death was strongly associated with functional impairment; 71% of families of decedents with ADL disability expected death, compared with 24% of those without ADL disability (P < .01). Death was expected more often in families of white decedents (60%) than African Americans (49%) (P < .01), although the effect of ADL disability was similar in both groups. After adjustment for potentially confounding factors, there were still significant associations between expecting death and functional impairment (odds ratio (OR) = 3.58, 95% confidence interval (CI) 2.73-4.70), and families of African Americans expected death less often than families of white decedents (OR = 0.63, 95% CI = 0.46-0.86).

CONCLUSION

Family members of older adults expected death only 58% of the time. Families of functionally impaired older people were more likely to expect death when it occurred than were families of older people who were not functionally impaired, and the expectation of death was lower for families of African Americans than for whites.

OBJECTIVES

To quantify the associations between sociodemographic factors and oral health-related quality of life (OHRQoL) in dentate and edentulous community-dwelling older adults.

DESIGN

Cross-sectional study using a 54-item OHRQoL questionnaire.

SETTING

Five counties in central Alabama: Jefferson and Tuscaloosa (urban), and Hale, Bibb, and Pickens (rural).

PARTICIPANTS

Two hundred eighty-eight participants (Dental Study subjects) aged 65 and older were recruited from participants in the University of Alabama at Birmingham Study of Aging, a longitudinal study of mobility in older African Americans and non-Hispanic whites.

MEASUREMENTS

Dental Study subjects were queried on their OHRQoL and sociodemographic status and classified into two categories: dentate and edentulous. Bivariate analyses were used to quantify associations between sociodemographic variables and OHRQoL after excluding participants with severe depression. Variables included age, sex, race, marital status, veteran status, residence, income, education, and transportation difficulties.

RESULTS

Dentate and edentulous subjects had similar OHRQoL across age, sex, marital status, veteran status, and residence. Analyses suggested a strong association between OHRQoL and race, education, income, and transportation difficulties in dentate subjects. Sociodemographic factors were less strongly associated with OHRQoL in edentulous participants.

CONCLUSION

OHRQoL decrements were prevalent in dentate and edentulous subjects. Of dentate persons, African Americans and those with a 6th-grade education or less, with income less than 16,000 dollars/year, and with transportation difficulties were more likely to have decrements in OHRQoL. In edentulous persons, these associations were not statistically significant or were weaker. These findings suggest differential associations between sociodemographic factors and OHRQoL when stratified according to dentate status.

Palliative care, with its focus on symptom management, patient-centered goals, preparation for life's end, and preservation of quality of life in the face of advancing illness, is a rapidly advancing component of mainstream American medicine. Yet, access to palliative care is often lacking in the community setting and may be further hindered by the presence of healthcare disparities that impact the poor. This article presents a unique approach to assuring the availability of palliative care to Medicaid patients receiving case management services. This descriptive article describes the evolution of a palliative care management pilot program, the Caring Connections Program, beginning with the initial planning and progressing through implementation and provision of services to 56 persons. "Lessons learned" are shared to enable other providers to develop similar programs with success. Patient profiles and intervention strategies are offered to illustrate the work accomplished.