Biomedical subjects

B Leake

Publications and source records attributed to B Leake.

At least 19 recordsLinked to original sources

PubMed2006

A randomized controlled trial of two treatment programs for homeless adults with latent tuberculosis infection.

SETTING: Few studies have examined strategies for optimizing adherence to latent tuberculosis infection (LTBI) treatment programs in homeless populations. OBJECTIVES: 1) To compare the effectiveness of an intervention program employing nurse case management and incentives (NCMI) vs. a control program with standard care and incentives on completion of LTBI treatment; and 2) to compare the impact of the two programs on tuberculosis (TB) knowledge among participants. DESIGN: A prospective, two-group site-randomized design conducted among 520 homeless adults residing in the Skid Row region of Los Angeles from 1998 to 2003, assessing completion rates of a 6-month isoniazid (INH) treatment program and change in TB knowledge. RESULTS: Using intent-to-treat analysis, 62% of participants in the intervention program, compared with 39% of controls, completed the full 6-month course of LTBI treatment with INH. Logistic regression modeling revealed that intervention participants had three times greater odds of completing INH treatment than controls. TB knowledge improved in both programs, but the increase was greater among the intervention participants (P < 0.001). CONCLUSIONS: Nurse case management combined with education, incentives, and tracking dramatically improves both adherence to LTBI treatment and TB knowledge in homeless persons compared to a standard approach of outreach and incentives.

Adult↗

PubMed2001

Comparison of psychosocial and behavioral profiles of victimized and nonvictimized homeless women and their intimate partners.

The purpose of this study was to examine the psychosocial, behavioral, and environmental profiles of homeless women, both those with and without a history of victimization, and their intimate partners. Five hundred seven homeless women and their intimate partners participated in the study. Thirty-nine percent of the women reported being physically and/or sexually assaulted as adults. Controlling for potential confounders, victimized women were more likely than others to have a history of childhood sexual and physical abuse, lifetime substance use, greater mental health symptomatology, and current risky sexual activity. Thus, homeless women with mental health and substance abuse problems ought to be screened for violent experiences and encouraged to obtain treatment appropriate to their problems to reduce their ongoing risk of victimization.

Adolescent↗

PubMed2001

Evaluating the impact of peer, nurse case-managed, and standard HIV risk-reduction programs on psychosocial and health-promoting behavioral outcomes among homeless women.

Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors (substance use and sexual risk behaviors) and cognitive and psychological resources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners. Participants were randomized by shelter to a peer-mentored, a nurse case-managed, or a standard care HIV risk-reduction program. Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological resources except for self-esteem. Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the standard group in self-esteem, life satisfaction, psychological well-being, use of noninjection drugs, sex with multiple partners, and unprotected sex at 6 months (n = 633). It was concluded that a standard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implications. Further, the impact of short-term programs that address psychological vulnerabilities of impoverished populations needs to be studied further.

Adolescent↗

PubMed2001

Hepatitis B among homeless and other impoverished US military veterans in residential care in Los Angeles.

Findings are presented for a cross-sectional study of serological markers of hepatitis B virus (HBV) infection in an underserved population-impoverished veterans of the US armed forces in a Veterans Administration (VA) residential program in the US. We examine the demographic, background, and risk factors associated with HBV infection in this high-risk population. This paper presents a secondary analysis of cross-sectional survey and clinical data for 370 male veterans who were residents of a domiciliary care program for homeless veterans in Los Angeles, using chi(2), Fisher's Exact, and logistic regression analysis. About one-third (30.8%) of the sample tested positive for current or past HBV infection (ie, seropositive for either the HBV core antibody or surface antigen). After multivariate analysis, rates of HBV were significantly higher among veterans who were older, non-white, or who had a history of regular heroin use (a proxy measure for injection drug use), drug overdose, or drug detoxification treatment. The rate of current or past HBV infection among veterans in this sample (30.8%) was high compared to an estimated 5% to 8% of the general US population. Also, 3% of the sample were currently infected with HBV. Strategies for intervention include broader screening, immunization, and treatment interventions with this high-risk group.

Adult↗

PubMed2000

Sheltered versus nonsheltered homeless women differences in health, behavior, victimization, and utilization of care.

OBJECTIVE: To contrast sociodemographic characteristics, physical and mental health status, substance use, sexual behaviors, victimization, and utilization of health services between homeless women residing in sheltered and non-sheltered environments. DESIGN: Cross-sectional survey. A structured scale was used to measure mental health status. Physical health status, substance use, sexual behavior, history of adult victimization, and health services utilization were measured by content-specific items. SETTING: Shelters (N = 47) and outdoor locations in Los Angeles. PARTICIPANTS: One thousand fifty-one homeless women. RESULTS: Homeless women living on the streets were more likely than sheltered women to be white and longer-term homeless. Controlling for sociodemographic characteristics, multiple logistic regression analyses revealed that unsheltered women had over 3 times greater odds of fair or poor physical health, and over 12 times greater odds of poor mental health than sheltered homeless women. They were also more likely than sheltered women to report using alcohol or noninjection drugs, to have multiple sexual partners, and to have a history of physical assault. About half of the overall sample reported utilization of a variety of health services; however, unsheltered homeless women were less likely to utilize all of the health services that were assessed, including drug treatment. CONCLUSIONS: There is a critical need for aggressive outreach programs that provide mental health services and substance abuse treatment for homeless women on the streets. Comprehensive services that also include medical care, family planning, violence prevention, and behavioral risk reduction may be particularly valuable for homeless women, especially those living in unsheltered environments.

Adult↗

PubMed2000

Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes.

HIV protease inhibitors have proven remarkably effective in treating HIV-1 infection. However, some tissues such as the brain and testes (sanctuary sites) are possibly protected from exposure to HIV protease inhibitors due to drug entry being limited by the membrane efflux transporter P-glycoprotein, located in the capillary endothelium. Intravenous administration of the novel and potent P-glycoprotein inhibitor LY-335979 to mice (1-50 mg/kg) increased brain and testes concentration of [(14)C]nelfinavir, up to 37- and 4-fold, respectively, in a dose-dependent fashion. Similar effects in brain levels were also observed with (14)C-labeled amprenavir, indinavir, and saquinavir. Because [(14)C]nelfinavir plasma drug levels were only modestly increased by LY-335979, the increase in brain/plasma and testes/plasma ratios of 14- to 17- and 2- to 5-fold, respectively, was due to increased tissue penetration. Less potent P-glycoprotein inhibitors like valspodar (PSC-833), cyclosporin A, and ketoconazole, as well as quinidine and verapamil, had modest or little effect on brain/plasma ratios but increased plasma nelfinavir concentrations due to inhibition of CYP3A-mediated metabolism. Collectively, these findings provide "proof-of-concept" for increasing HIV protease inhibitor distribution into pharmacologic sanctuary sites by targeted inhibition of P-glycoprotein using selective and potent agents and suggest a new therapeutic strategy to reduce HIV-1 viral replication.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Human MRP3 transporter: identification of the 5'-flanking region, genomic organization and alternative splice variants.

In humans, at least six members of the multidrug resistance-associated protein (MRP) family are thought to exist. Here we report the molecular cloning of two splice variants of MRP3 from human liver. In addition, MRP3 genomic organization including the 5'-flanking region and a major portion of the MRP3 intron-exon organization are identified and characterized.

ATP-Binding Cassette Transporters↗

PubMed1999

Associations between homeless women's intimate relationships and their health and well-being.

The purpose of this study was to describe the associations between intimate relationships, characterized in terms of presence or absence of conflictive interaction with the partner, and the health and well-being of homeless women. A sample of 558 homeless women were administered structured interviews by trained nurses or outreach workers of the participants' ethnicity. Women answered questions about their general physical health, health-threatening behaviors (i.e., risky drug and sexual behaviors), health-promoting behaviors (i.e., TB and Pap testing), psychological well-being and symptomatology, self-esteem, coping, and life satisfaction. Women in nonconflictive relationships reported significantly greater psychological well-being, self-esteem, and life satisfaction and less hostility and noninjection drug use than women with conflictive relationships or those without an intimate partner. Women with conflictive relationships were significantly more anxious and depressed than those with nonconflictive relationships. Results suggest that, when possible, it is advisable to involve the intimate partner in programs to facilitate the emotional well-being of homeless women.

Adaptation, Psychological↗

PubMed1999

Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein.

PURPOSE: CYP3A and P-gp both function to reduce the intracellular concentration of drug substrates, one by metabolism and the other by transmembrane efflux. Moreover, it has been serendipitously noted that the two proteins have many common substrates and inhibitors. In order to test this notion more fully, systematic studies were undertaken to determine the P-gp-mediated transport and inhibitory characteristics of prototypical CYP substrates. METHODS: L-MDR1, LLC-PK1, and Caco-2 cells were used to evaluate established CYP substrates as potential P-gp substrates and inhibitors in vitro, and mdr1a deficient mice were used to assess the in vivo relevance of P-gp-mediated transport. RESULTS: Some (terfenadine, erythromycin and lovastatin) but not all (nifedipine and midazolam) CYP3A substrates were found to be P-gp substrates. Except for debrisoquine, none of the prototypical substrates of other common human CYP isoforms were transported by P-gp. Studies in mdr1a disrupted mice confirmed that erythromycin was a P-gp substrate but the CYP3A-inhibitor ketoconazole was not. In addition, CYP3A substrates and inhibitors varied widely in their ability to inhibit the P-gp-mediated transport of digoxin. CONCLUSIONS: These results indicate that the overlap in substrate specificities of CYP3A and P-gp appears to be fortuitous rather than indicative of a more fundamental relationship.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Two-year follow-up of AIDS education programs for impoverished women.

The long-term effects of two culturally competent AIDS education programs with different content on the risk behavior and AIDS-related knowledge of 410 homeless African American women 2 years after program completion were examined. Participants were members of a larger cohort of impoverished African American and Latina women recruited in Los Angeles from 1989 to 1991. Of a subsample of 527 African American women selected randomly for a 2-year follow-up interview, 410 (78%) were located and agreed to participate. Women participating in both AIDS education programs reported reduced HIV risk behaviors and demonstrated greatly improved AIDS knowledge at 2-year follow-up (p < .001). Women in a specialized program were less likely than those in a traditional program to report noninjection drug use at 2 years. Women in the traditional program had significantly better AIDS knowledge at follow-up (p < .001). These findings suggest that educational programs can produce sustained benefits among impoverished women.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Perceived factors influencing the initiation of drug and alcohol use among homeless women and reported consequences of use.

A qualitative research approach was used to explore the factors that influence the initiation of drug and alcohol use among homeless women and the health and social consequences of drug and alcohol use. The sample consisted of 238 women; of whom 209 women reported drug and/or alcohol use in the past month and 29 women reported no history of drug or alcohol use. Findings of the study revealed homeless women who currently used drugs and alcohol, homeless women who currently used drugs only, and to a lesser extent current alcohol users only, had suffered traumatic childhood events and family dysfunction and had to cope with low self-esteem, emotional distress, and poor physical health. The initiation of drug and/or alcohol use was strongly affected by the social influence of other users. In comparison, homeless women who did not use drugs or alcohol reported a positive self-image, few traumatic events, and chose partners who did not use drugs or alcohol. Common among current drug and/or alcohol users were the reported social benefits of drug use. Quantitative analyses revealed homeless women who were current drug users were significantly more likely to have experienced childhood and adult victimization as compared with women in the other groups. Thus, the need for social interventions and positive social support early in the lives of these women are strongly implicated in these findings.

Adult↗

PubMed1999

OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.

Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition. Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake. On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. In addition, oral and i.v. administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice. Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.

Adequate bile flow, maintained in part by the efficient enterohepatic recirculation of bile acids, is critical for normal liver function. One important component of this process is the uptake of bile acids from the portal circulation into hepatocytes by the bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP). Thus, the expression and functional activity of this transporter may affect the rate of bile acid removal from the portal circulation. Accordingly, we assessed NTCP mRNA expression from human livers using a sensitive RNase protection assay. In addition, the ability of various bile acids and drugs to inhibit NTCP activity was determined using a recombinant vaccinia expression system. A 40-fold interindividual variability was found in NTCP mRNA levels determined in eight liver samples of disease-free donors. Expressed NTCP exhibited high-affinity, sodium-dependent uptake of taurocholate, and as expected, this was markedly inhibited by bile acids and organic anions. A number of drugs, including peptidomimetic renin inhibitors, propranolol, cyclosporin, and progesterone, were found to be potent inhibitors, whereas antiarrhythmic agents, including bupivicaine, lidocaine, and quinidine, were found to enhance NTCP activity. Accordingly, these results indicate that large interindividual variability exists in NTCP mRNA level and that a number of drugs currently in clinical use have the potential to interact with and alter NTCP activity, thereby affecting hepatic bile acid uptake.

Bile Acids and Salts↗

PubMed1998

The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.

Currently available HIV-1 protease inhibitors are potent agents in the therapy of HIV-1 infection. However, limited oral absorption and variable tissue distribution, both of which are largely unexplained, complicate their use. We tested the hypothesis that P-glycoprotein is an important transporter for these agents. We studied the vectorial transport characteristics of indinavir, nelfinavir, and saquinavir in vitro using the model P-glycoprotein expressing cell lines L-MDR1 and Caco-2 cells, and in vivo after intravenous and oral administration of these agents to mice with a disrupted mdr1a gene. All three compounds were found to be transported by P-glycoprotein in vitro. After oral administration, plasma concentrations were elevated 2-5-fold in mdr1a (-/-) mice and with intravenous administration, brain concentrations were elevated 7-36-fold. These data demonstrate that P-glycoprotein limits the oral bioavailability and penetration of these agents into the brain. This raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic inhibition of P-glycoprotein transport activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Tuberculosis in homeless patients: potential for case finding in public emergency departments.

STUDY OBJECTIVES: Previous studies have had difficulty evaluating the optimal clinical site for screening homeless patients for active tuberculosis (TB). We hypothesized that homeless patients with TB would not frequently reside in shelters at the time of their diagnosis and would be more likely than other patients with TB to seek care in public hospitals, thus presenting an opportunity for screening radiography. METHODS: This registry-based survey included 743 consecutive patients with confirmed active TB in Los Angeles County. No therapeutic intervention was involved. RESULTS: When compared with patients with TB who were not homeless, homeless patients with TB were more likely to be male (93% versus 63%, P<.001), black (44% versus 15%, P<.001), living in the inner city (55% versus 7%, P<.001), and born in the United States (67% versus 32%, P<.001). They were more infectious than other patients with TB as evidenced by a trend toward more cavitary radiographic lesions (24% versus 16%, P=.11) and significantly more positive sputum smears (56% versus 41%, P=.009). Less than a third lived in congregate facilities such as shelters at the time of their diagnosis. Instead, their disease was diagnosed more often at county hospitals (54% versus 23%, P<.001) than patients with TB who were not homeless. CONCLUSION: Widespread screening for TB in shelters may miss most homeless patients with TB. Because most county-hospital homeless patients with TB initially present to emergency departments and many do not live in shelters, future cost-effectiveness studies should evaluate chest radiograph screening for all homeless ED patients.

Adult↗

PubMed1998

The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure.

OBJECTIVES: The need for accurate measures of health-related quality of life (HRQOL) in men treated for prostate cancer is of paramount importance because patients may survive for many years after their diagnosis. Hence, interest has increased in choosing treatments that optimize both the quality and quantity of life in patients with this disease. This study sought to develop and evaluate a self-administered, multiitem, disease-specific instrument to capture the health concerns central to the quality of life of men treated for early stage prostate cancer. METHODS: After focus group analysis and pilot testing, the instrument was tested with a large retrospective, cross-sectional survey. Exploratory factor analysis and multitrait scaling analysis were used to facilitate the formation of six scales containing 20 disease-targeted items that address impairment in the urinary, bowel, and sexual domains. The psychometric properties of the new scales were assessed by measuring test-retest reliability, internal consistency reliability, and construct validity. Performance on the new scales was compared with scores on other established cancer-related health-related quality of life instruments. Two hundred fifty-five long-term survivors of prostate cancer treatment and 273 age-matched and ZIP code-matched comparison subjects without prostate cancer from a large managed care population in California were studied. Mean age was 72.7 years. In addition to the new scales, the RAND 36-Item Health Survey (SF-36) was used as a generic core measure, and a cancer-related health-related quality of life instrument (the Cancer Rehabilitation System-Short Form) was used to provide construct validity. RESULTS: For the new scales, test-retest reliability ranged from 0.66 to 0.93, and internal consistency ranged from 0.65 to 0.93. Disease-targeted measures of function and bother in the three domains correlated substantially with one another. Scale scores correlated well with related, established scales. Men undergoing prostatectomy or pelvic irradiation demonstrated the expected differences in performance on the disease-specific health-related quality of life scales when compared with each other or with comparison subjects. Age was inversely related to sexual and bowel function. CONCLUSIONS: The UCLA Prostate Cancer Index performed well in this population of older men with and without prostate cancer. It demonstrated good psychometric properties and appeared to be well understood and easily completed. The high response among patients suggests that these men especially are interested in addressing both the general and disease-specific concerns that impact their daily quality of life.

Aged↗

PubMed1998

Why do symptomatic patients delay obtaining care for tuberculosis?

The resurgence of tuberculosis (TB) has coincided with deteriorating access to care for high-risk populations. We sought to determine what perceived access barriers delayed symptomatic TB patients from obtaining care. In order to do this, we conducted a survey in Los Angeles County, California, using a consecutive sample of patients with active TB as confirmed by the county TB control authority. The measures used in the study were a self-reported delay in seeking care of more than 60 d from symptom onset, a period sufficient to cause skin-test conversion in exposed contacts, and self-reported access barriers. The county TB registry provided supplementary clinical data. We found that one in five of the 248 symptomatic respondents (response rate: 60%) delayed obtaining care for > 60 d (mean = 74 d, SD = 216 d). During the delay, patients exposed an average of eight contacts. As compared with the rest of the sample, delay was more common in those who were unemployed (25% versus 14%), concerned about cost (27% versus 14%), anticipated prolonged waiting-room time (26% versus 14%), believed they could treat themselves (31% versus 14%), anticipated difficulty in getting an appointment (28% versus 16%), were uncertain about where to get care (33% versus 16%), and feared immigration authorities (47% versus 18%) (p < 0.05). Logistic regression revealed that uncertainty about where to get care, unemployment, and belief in the efficacy of self-treatment independently predicted delay > 60 d. Illness severity as measured by chest radiography, sputum smears, and symptoms had little impact on delay. We conclude that because access variables such as lack of employment and knowledge about where to obtain care were more closely associated with clinically significant delay than was severity of illness, these results raise concerns about the equity of access to care among TB patients. The results suggest that improving the availability of services for high-risk groups may substantially reduce TB patients' delay in obtaining care, and thus may limit the spread of the disease.

Adult↗

PubMed1998

Effectiveness of a specialized vs. traditional AIDS education program attended by homeless and drug-addicted women alone or with supportive persons.

This research examined the impact of including a supportive person on the outcomes of two culturally sensitive AIDS education programs, an education-only (traditional) program and a program combining education with self-esteem and coping enhancement (specialized). Research participants in this quasi-experimental study included 241 homeless women, who were randomly assigned by residence (drug treatment program or shelter) to one of four treatment groups. The outcomes measured at baseline, 6, and 12 months were risk behaviors, cognitive factors, and psychological functioning. Study results demonstrated significant improvements at both 6 and 12 months for the entire sample in all psychological, behavioral and cognitive outcome variables except active coping. Women in the specialized program improved more on AIDS knowledge and reduction in non-injection drug use than did those in the traditional program, but their active coping scores declined. Participation of a supportive person did not appear to have any effect on outcome.

Acquired Immunodeficiency Syndrome↗