Publications

OBJECTIVE

To identify the prevalence of disability in a wide range of valued life activities (VLAs) among individuals with systemic lupus erythematosus (SLE), 1-year changes in such disability, and predictors of and changes in VLA disability.

METHODS

Data were from 2 waves of a cohort of 829 individuals with SLE interviewed annually by telephone. VLA disability was assessed using a scale rating the difficulty of performing 21 activities. Scores were also calculated for subscales corresponding to obligatory, committed, and discretionary activities. Changes in VLA disability from baseline to 1-year followup were assessed. Sociodemographic and disease status measures were examined as predictors of and changes in VLA disability using multiple regression analyses.

RESULTS

Almost half of the subjects were unable to perform > or =1 VLA at baseline. Almost all (91%) reported > or =1 VLA affected by SLE. One-quarter of the subjects experienced a significant increase in the number of activities they were unable to perform; approximately half experienced significant increases in the number of activities affected and in difficulty scores. Proportions of individuals whose disability increased and whose disability decreased were roughly equivalent. Disease status measures accounted for 62-72% of the variation in VLA difficulty. More severe disease status was predictive of increases in VLA difficulty; few predictors of improvements were identified.

CONCLUSION

VLA disability was common, with more disability noted in committed and discretionary activities than in obligatory activities. Because VLA disability has been linked to psychological well-being in previous studies, identification of factors that may protect against such disability is important.

OBJECTIVE

To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations.

DESIGN

Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1-infected subjects divided into 3 groups: not on ART (termed "offs"), on ART with plasma HIV-1 RNA >500 copies/mL ("failures"), and on ART with plasma HIV-1 RNA

RESULTS

CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels.

CONCLUSIONS

The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels.

BACKGROUND

We measured the perception of breast, cervical, and colon cancer risks and screening in diverse women to examine the association between risk perception and screening behavior.

METHODS

Cross-sectional telephone and in-person interviews of women aged 50 to 80 years were conducted in English, Spanish, or Chinese. The women were recruited from primary care practices in San Francisco, California (academic general internal medicine, family medicine, women's health practices, a community-based clinic in Chinatown, and the Community Health Network Clinics, which is affiliated with the San Francisco Department of Public Health), with at least 1 visit within the previous 2 years. Perceived personal risk for each cancer was measured on a word scale (no risk to very high risk) and compared with self-reported screening behavior by ethnicity.

RESULTS

A total of 1160 women participated: 338 (29%) were White, 167 (14%) were African American, 239 (21%) were Latina, and 416 (36%)were Asian. The average participant was 61 years old and a high school graduate; 18% had a personal history of cancer, and 42% had a family history of cancer. The perceived lifetime risk of cancer varied by ethnicity. Compared with White women, Latinas had a higher perceived risk for cervical cancer (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.8-4.6) and colon cancer (OR, 3.0; 95% CI, 1.8-5.0) after multivariate adjustment, and Asians had a lower perceived risk for cervical cancer (OR, 0.6; 95% CI, 0.4-0.9) and colon cancer (OR, 0.6; 95% CI, 0.3-0.9). Higher colon cancer risk perception was associated with having undergone colonoscopy within 10 years (OR, 2.8; 95% CI, 1.4-5.4).

CONCLUSIONS

Risk perception was significantly associated with colon cancer screening behavior (P=.001). Evaluation of patients' perceived risk of cancer may be useful to clinicians who are recommending screening tests.

Mutations in the chloroquine resistance (CQR) transporter gene of Plasmodium falciparum (Pfcrt; chromosome 7) play a key role in CQR, while mutations in the multidrug resistance gene (Pfmdr1; chromosome 5) play a significant role in the parasite's resistance to a variety of antimalarials and also modulate CQR. To compare patterns of genetic variation at Pfcrt and Pfmdr1 loci, we investigated 460 blood samples from P. falciparum-infected patients from four Asian, three African, and three South American countries, analyzing microsatellite (MS) loci flanking Pfcrt (five loci [approximately 40 kb]) and Pfmdr1 (either two loci [approximately 5 kb] or four loci [approximately 10 kb]). CQR Pfmdr1 allele-associated MS haplotypes showed considerably higher genetic diversity and higher levels of subdivision than CQR Pfcrt allele-associated MS haplotypes in both Asian and African parasite populations. However, both Pfcrt and Pfmdr1 MS haplotypes showed similar levels of low diversity in South American parasite populations. Median-joining network analyses showed that the Pfcrt MS haplotypes correlated well with geography and CQR Pfcrt alleles, whereas there was no distinct Pfmdr1 MS haplotype that correlated with geography and/or CQR Pfmdr1 alleles. Furthermore, multiple independent origins of CQR Pfmdr1 alleles in Asia and Africa were inferred. These results suggest that variation at Pfcrt and Pfmdr1 loci in both Asian and African parasite populations is generated and/or maintained via substantially different mechanisms. Since Pfmdr1 mutations may be associated with resistance to artemisinin combination therapies that are replacing CQ, particularly in Africa, it is important to determine if, and how, the genetic characteristics of this locus change over time.

BACKGROUND

We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB.

METHODS

Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays.

RESULTS

Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p < 0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p < 0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p > 0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months.

CONCLUSIONS

LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term.