Publications

In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe steatorrhea is often documented. However, pancreatic exocrine secretion has not yet been studied. In 14 children with PFIC-2, pancreatic function was assessed using standard fecal tests. Normal fecal lipase concentrations excluded isolated lipase deficiency. No differences in fecal elastase-1 concentrations and chymotrypsin activities were detected between PFIC-2 patients with or without steatorrhea, nor between these patients and healthy subjects. In conclusion, pancreatic exocrine function in patients with PFIC-2 is normal. Steatorrhea observed in those patients is not related to pancreatic insufficiency.

OBJECTIVES

To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons.

DESIGN

Prospective diet intervention study.

SETTING

University of Washington Medical Center from 2001 through 2005.

PARTICIPANTS

Twenty-one younger (18-35) and 18 older (> or =70) men and women.

INTERVENTION

Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake.

MEASUREMENTS

Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured.

RESULTS

Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed.

CONCLUSION

Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

OBJECTIVE

Although prior research demonstrated that improving diabetes self-efficacy can improve self-management behavior, little is known about the applicability of this research across race/ethnicity and health literacy levels. We examined the relationship between diabetes self-efficacy and self-management behavior in an urban, diverse, low-income population with a high prevalence of limited health literacy.

RESEARCH DESIGN AND METHODS

We administered an oral questionnaire in Spanish and English to patients with type 2 diabetes at two primary care clinics at a public hospital. We measured self-efficacy, health literacy, and self-management behaviors using established instruments. We performed multivariate regressions to explore the associations between self-efficacy and self-management, adjusting for clinical and demographic factors. We tested for interactions between self-efficacy, race/ethnicity, and health literacy on self-management.

RESULTS

The study participants were ethnically diverse (18% Asian/Pacific Islander, 25% African American, 42% Latino/a, and 15% white), and 52% had limited health literacy (short version of the Test of Functional Health Literacy in Adults score <23). Diabetes self-efficacy was associated with four of the five self-management domains (P < 0.01). After adjustment, with each 10% increase in self-efficacy score, patients were more likely to report optimal diet (0.14 day more per week), exercise (0.09 day more per week), self-monitoring of blood glucose (odds ratio 1.16), and foot care (1.22), but not medication adherence (1.10, P = 0.40). The associations between self-efficacy and self-management were consistent across race/ethnicity and health literacy levels.

CONCLUSIONS

Self-efficacy was associated with self-management behaviors in this vulnerable population, across both race/ethnicity and health literacy levels. However, the magnitude of the associations suggests that, among diverse populations, further study of the determinants of and barriers to self-management is warranted. Policy efforts should be focused on expanding the reach of self-management interventions to include ethnically diverse populations across the spectrum of health literacy.

Among individuals receiving highly active antiretroviral therapy (HAART), injection drug users (IDUs) are less likely to achieve HIV suppression. The present study examined individual-level, interpersonal, and structural factors associated with achieving undetectable plasma viral load (UVL) among US IDUs receiving recommended HAART. Data were from baseline assessments of the INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4-site, secondary HIV prevention intervention for heterosexually active IDUs. Of 1113 study participants at baseline, 42% (n = 466) were currently taking recommended HAART (34% were female, 69% non-Hispanic black, 26% recently homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic regression revealed that among those on recommended HAART, adjusted odds of UVL were at least 3 times higher among those with high social support, stable housing, and CD4 > 200; UVL was approximately 60% higher among those reporting better patient-provider communication. Outpatient drug treatment and non-Hispanic black race and an interaction between current drug use and social support were marginally negatively significant. Among those with high perceived support, noncurrent drug users compared with current drug users had a greater likelihood of UVL; current drug use was not associated with UVL among those with low support. Depressive symptoms (Brief Symptom Inventory) were not significant. Results suggest the major role of social support in facilitating effective HAART use in this population and suggest that active drug use may interfere with HAART use by adversely affecting social support. Interventions promoting social support functioning, patient-provider communication, stable housing, and drug abuse treatment may facilitate effective HAART use in this vulnerable population.

An alpha1-adrenergic receptor (alpha1-AR) antagonist increased heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to alpha1-AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main alpha1-AR subtypes in the heart, alpha 1A (Adra1a) and alpha 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and beta-AR stimulation, and beta-ARs were desensitized. Thus, alpha1-AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that alpha1-signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of alpha1-antagonists in clinical trials are due to loss of alpha1-signaling in myocytes, emphasizing concern about clinical use of alpha1-antagonists, and point to a revised perspective on sympathetic activation in heart failure.

OBJECTIVE

Percent fat is often considered the reference for establishing the magnitude of adipose tissue accumulation and the risk of excess adiposity. However, the increasing recognition of a strong link between central adiposity and metabolic disturbances led us to test whether waist circumference (WC) is more highly correlated with metabolic syndrome components than percent fat and other related anthropometric measures such as BMI.

RESEARCH METHODS AND PROCEDURES

BMI, WC, and percent fat, measured by DXA, were evaluated in 1010 healthy white and African-American men and women [age, 48.3 +/- 17.2 (standard deviation) years; BMI, 27.0 +/- 5.3 kg/m(2)]. The associations of BMI, WC, and percent fat with age and laboratory-adjusted health risk indicators (i.e., serum glucose, insulin, triglycerides, high-density lipoprotein cholesterol, blood pressure) in each sex and ethnicity group were examined.

RESULTS

For 18 of 24 comparisons, the age- and laboratory-adjusted correlations were lowest for percent fat and in 16 of 24 comparisons were highest for WC. Fifteen of the between-method differences reached statistical significance. With health risk indicator as the dependent variable and anthropometric measures as the independent variable, the contribution of percent fat to the WC regression model was not statistically significant; in contrast, adding WC to the percent fat regression model did make a significant independent contribution for most health risk indicators.

DISCUSSION

WC had the strongest associations with health risk indicators, followed by BMI. Although percent fat is a useful measure of overall adiposity, health risks are best represented by the simply measured WC.

OBJECTIVE

The objective of this study was to investigate the relationship between sex work and HIV infection among young injection drug-using men who have sex with men (MSM-IDU).

STUDY DESIGN

This study was a cross-sectional analysis of behavioral and serologic data collected from 227 street-recruited MSM-IDU in San Francisco, California, between January 2000 and November 2001.

RESULTS

Sixty-eight percent of participants reported being paid by another man for sex. HIV prevalence was 12% (95% confidence interval, 8-16%); 42% of seropositive participants were unaware of their infection. HIV was independently associated with higher number of paying male partners and history of gonorrhea and inversely associated with number of female partners, education, and syringe-sharing. Consistent condom use overall was 41%, but varied significantly by type of partner.

CONCLUSIONS

Among MSM-IDU in San Francisco, sex work with men is strongly associated with HIV infection and the prevalence of condom use is low. HIV prevention among MSM-IDU must be tailored to address the excess risk associated with sex work.

OBJECTIVES

This study examined the association between genetic polymorphisms and enzyme activity for antioxidant enzymes that share a common detoxification pathway: manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1) and catalase.

METHODS

MnSOD, GPX1, and catalase activities were measured in isolated erythrocytes of 231 healthy, non-smoking student volunteers (55% women, ages 17-21, majority Asian or Caucasian). DNA from blood clots was genotyped by Taqman PCR (C47T : MnSOD and C593T : GPX1) and standard PCR (-262C>T : catalase). Associations between genotype and enzyme activity were analyzed by multiple linear regression, adjusted for baseline factors including gender and ethnicity.

RESULTS

Minor allele frequencies ranged from 13% for catalase (T) to 18% for GPX1 (T), and 33% for MnSOD(C) with significant variation between ethnicities. Median GPX1 activity was 13.2 U/g Hb with a six-fold difference between lowest and highest levels. Catalase activity ranged eight-fold (median: 86.3 k/g Hb), while median MnSOD activity was 2.8 U/mg Hb with a 56-fold range of values. MnSOD enzyme activity was 15% higher in females than males (95%CI : -1%, 32%), and 33% higher in CT or TT individuals (C47T) versus CC individuals (95%CI : 7-59%). On average, catalase activity was 18.1 k/g Hb lower for TT subjects (-262C>T) versus CC subjects (95% CI: -32.3, -4.0). All enzyme activities were correlated (r=0.3-0.4, P<0.001).

CONCLUSIONS

Interindividual variability of antioxidant enzyme activity in healthy young adults was partially explained by significant associations with three known genetic polymorphisms, and was further modified by gender and ethnicity. A substantial component of this variability may be attributable to differences in diet, environmental exposures, and additional genetic factors.

The genotype frequencies of MDR1 T-129C, C1236T, G2677A,T and C3435T SNPs were compared in 154 healthy Japanese and 100 healthy Caucasians to provide basic information on the inter-ethnic differences of pharmacotherapeutic outcome. The variants were found at allelic frequencies of 5.5%, 65.6%, 16.6%, 40.6% and 40.6%, for T-129C, C1236T, G2677A, G2677T and C3435T, respectively, in Japanese, and at 5.1%, 45.9%, 3.6%, 46.4% and 56.6%, respectively, in Caucasians, with a statistically significant difference for C1236T, G2677A,T and C3435T (p<0.001). G2677A was about 5-fold more frequent in Japanese than Caucasians. These genotype frequencies were also investigated in 95 Japanese patients with colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC), but no significant difference was detected, when compared with healthy Japanese subjects. The haplotype frequency reached a total of about 85% in Japanese with the following 4 major haplotypes; T(-129)-T1236-T2677-T3435 (36.1%), T(-129)-T1236-G2677-C3435 (22.5%), T(-129)-C1236-G2677-C3435 (14.2%) and T(-129)-C1236-A2677-C3435 (13.3%). The second and fourth haplotypes were hardly inferred in Caucasian, whereas T(-129)-C1236-G2677-T3435 (12.8%) was found to be Caucasian-specific. There was a tendency for higher frequencies of the T(-129)/C-(129)-C1236-A2677-C3435 haplotype in Japanese CRC patients and T(-129)-T1236-T2677-T3435 haplotype in Japanese ESCC patients, compared with that in healthy Japanese subjects.

The number of older prisoners is increasing exponentially. For example, the number of geriatric female prisoners in California has increased 350% in the past decade. Despite an increasing population of geriatric female prisoners, the degree of functional impairment in this population is unknown. Therefore, the goals of this study were to describe the prevalence and nature of functional impairment in geriatric female prisoners in California and to identify aspects of the prison environment that may exacerbate functional impairments. Questionnaires were analyzed from 120 geriatric women in California state prisons. Functional impairment was defined as impairment in activities of daily living (ADLs) or in prison ADLs (PADLs), including dropping to the floor for alarms, standing for count, getting to meals, hearing orders, and climbing onto the top bunk. The mean age of participants was 62; 16% were dependent in one ADL, and 69% reported one PADL impairment. Increasing severity of functional impairment was associated with worse health status and more adverse prison experiences. For example, fall rates ranged from 33% in women without impairment to 57% with PADL impairment to 63% with ADL dependence (P=.02). Several prison environmental stressors were identified that likely exacerbate functional impairment. For example, 29% of geriatric women were assigned to a top bunk. Geriatric female prisoners report high rates of functional impairment. ADL and PADL impairment were associated with worse health status and adverse prison experiences. Therefore, the evaluation of functional impairment in geriatric female prisoners needs to consider the unique demands of the prison environment.