Publications

Observations on the association between exposure to common outdoor air pollutants and allergic sensitization have not been consistent. Little research has been done on the effects of prenatal exposure or the effect among asthmatics. The association between prenatal and early-life exposures and outdoor air pollutants with allergic sensitization was examined within a cohort of 170 children ages 6-11 years with asthma, living in the Central Valley of California. Allergic sensitization was ascertained by skin-prick tests to 14 allergens. Prenatal and early-life exposure to ozone (O(3)), nitrogen dioxide (NO(2)), carbon monoxide (CO) and particulate matter with a median aerodynamic diameter < 10 micro m (PM(10)) was reconstructed for each child. Models were developed for sensitized to (a) any allergen, (b) at least one outdoor allergen, and (c) at least one indoor allergen. In multivariable analyses, higher exposure to CO during pregnancy was associated with an increased risk of sensitization to at least one outdoor allergen. The largest effect was seen for the association between exposure to 8-hour daily maximum CO during pregnancy and sensitization to at least one outdoor allergen. (OR = 1.55 (95% CI: 1.01, 2.37)) per interquartile range (IQR) increase.) Similar effects estimates were seen for 2nd trimester exposure to CO, but these were less precisely estimated (OR = 1.45 (95%CI: 0.90, 2.35)). No significant associations with the pollutants were seen for sensitization to allergens in general or to at least one indoor allergen. Exposure to traffic-related pollutants during pregnancy may increase the risk of sensitization to outdoor allergens among asthmatic children.

Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. In this study, we defined the HIV epitopes targeted by 76 pediatric subjects (47 HIV infected and 29 HIV exposed, but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFN-gamma, TNF-alpha, and IL-2. No responses were detected among HIV-uninfected infants, whereas responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 mo old (p = 0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (log viral load 5.8 vs 5.0; p = 0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 mo of age, and that HIV-specific CD4 cell responses were of universally low frequency among antiretroviral-naive children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV.

U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 ancestry informative markers in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco Bay area and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (95% CI) for ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European ancestry was associated with increased breast cancer risk. The OR for a 25% increase in European ancestry was 1.79 (95% CI, 1.28-2.79; P<0.001). When known risk factors and place of birth were adjusted for, the association with European ancestry was attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06-2.11; P=0.013). Further work is needed to determine if the association is due to genetic differences between populations or possibly due to environmental factors not measured.

BACKGROUND

As people live longer, there is increasing potential for mental disorders to interfere with testamentary distribution and render older people more vulnerable to "undue influence" when they are making a will. Accordingly, clinicians dealing with the mental disorders of older people will be called upon increasingly to advise the courts about a person's vulnerability to undue influence.

METHOD

A Subcommittee of the IPA Task Force on Testamentary Capacity and Undue Influence undertook to establish consensus on the definition of undue influence and the provision of guidelines for expert assessment of risk factors for undue influence.

RESULTS

International jurisdictions differ in their approach to the notion of undue influence. Despite differences in legal systems, from a clinical perspective, the subcommittee identified some common "red flags" which might alert the expert to risk of undue influence. These include: (i) social or environmental risk factors such as dependency, isolation, family conflict and recent bereavement; (ii) psychological and physical risk factors such as physical disability, deathbed wills, sexual bargaining, personality disorders, substance abuse and mental disorders including dementia, delirium, mood and paranoid disorders; and (iii) legal risk factors such as unnatural provisions in a will, or provisions not in keeping with previous wishes of the person making the will, and the instigation or procurement of a will by a beneficiary.

CONCLUSION

This review provides some guidance for experts who are requested by the courts to provide an opinion on the risk of undue influence. Whilst international jurisdictions require different thresholds of proof for a finding of undue influence, there is good international consensus on the clinical indicators for the concept.

BACKGROUND

Malaria epidemics in highland areas of Kenya cause significant morbidity and mortality.

METHODS

To assess treatment-seeking behaviour for malaria in these areas, a questionnaire was administered to 117 randomly selected households in the highland area of Kipsamoite, Kenya. Self-reported episodes of malaria occurred in 100 adults and 66 children.

RESULTS

The most frequent initial sources of treatment for malaria in adults and children were medical facilities (66.0% and 66.7%) and local shops (19.0% and 30.3%). Adults and children who initially visited a medical facility for treatment were significantly more likely to recover and require no further treatment than those who initially went to a local shop (adults, 84.9% v. 36.8%, P < 0.0001, and children, 79.6% v. 40.0%, P = 0.002, respectively). Individuals who attended medical facilities recalled receiving anti-malarial medication significantly more frequently than those who visited shops (adults, 100% vs. 29.4%, and children, 100% v. 5.0%, respectively, both P < 0.0001).

CONCLUSION

A significant proportion of this highland population chooses local shops for initial malaria treatment and receives inappropriate medication at these localshops, reslting in delay of effective treatment. Shopkeeper education has the potential to be a component of prevention or containment strategies for malaria epidemics in highland areas.

The retinal pigment epithelium (RPE) plays an important role in maintaining a healthy neural retina. With changes due to age, morbidity or removal of choroidal neovascularis developed as a means ofation, damage or defects of the RPE occur. Accordingly, RPE transplantation techniques have been repairing the damaged RPE. We conducted a study to transplant tissue-engineered RPE cell sheets in a rabbit model. RPE cells were isolated from pigmented rabbit eyes and seeded on temperature-responsive culture surfaces. Cultured RPE cells were arranged as a monolayer with a cobblestone cell shape that is characteristic of native RPE. The pigmented RPE cell sheets were non-invasively harvested without enzymatic treatment simply by reducing the culture temperature. Using 3-port vitrectomy, RPE cell sheets were transplanted into the subretinal space of albino rabbits. Seven days after surgery, the rabbits were sacrificed, and the eyes were enucleated and examined under both light and electron microscopy. After transplantation, our results show that the RPE cell sheets attached to the host tissues in the subretinal space more effectively than with the injection of isolated cell suspensions. Although the cell sheets maintained a monolayer structure in most areas, they were slightly folded or wrinkled in some regions. We conclude that tissue-engineered RPE cell sheets harvested from temperature-responsive culture dishes can be effectively transplanted beneath the neural retina.