Publications

BACKGROUND

Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival.

METHODS

The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75.

RESULTS

Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior.

CONCLUSIONS

These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Cytochrome P450, CYP3A4, is the dominant human liver endoplasmic reticulum (ER) hemoprotein enzyme, responsible for the metabolism of over 60% of clinically relevant drugs. We have previously shown that mechanism-based suicide inactivation of CYP3A4 and its rat liver ER orthologs, CYPs 3A, via heme-modification of their protein moieties, results in their ubiquitin (Ub)-dependent 26S proteasomal degradation (Korsmeyer et al. (1999) Arch. Biochem. Biophys. 365, 31; Wang et al. (1999) Arch. Biochem. Biophys. 365, 45). This is not surprising given that the heme-modified CYP3A proteins are structurally damaged. To determine whether the turnover of the native enzyme similarly recruited this pathway, we heterologously expressed this protein in wild-type Saccharomyces cerevisiae and mutant strains (hrd1Delta, hrd2-1, and hrd3Delta) previously shown to be deficient in the Ub-dependent 26S proteasomal degradation of the polytopic ER protein 3-hydroxy-3-methylglutaryl-CoA reductase (isoform Hmg2p), the rate-limiting enzyme in sterol biosynthesis, as well as in strains deficient in ER-associated Ub-conjugating enzymes, Ubc6p and/or Ubc7p (Hampton et al. (1996) Mol. Biol. Cell 7, 2029; Hampton and Bhakta (1997) Proc. Natl. Acad. Sci. USA 94, 12,944). Our findings reveal that in common with the degradation of Hmg2p, that of native CYP3A4 also requires Hrd2p (a subunit of the 19S cap complex of the 26S proteasome) and Ubc7p, and to a much lesser extent Hrd3p, a component of the ER-associated Ub-ligase complex. In contrast to Hmg2p-degradation, that of native CYP3A4 does not appear to absolutely require Hrd1p, another component of the ER-associated Ub-ligase complex. Furthermore, studies in a S. cerevisiae pep4Delta strain proven to be deficient in the vacuolar degradation of carboxypeptidase Y indicated that CYP3A4 degradation is also largely independent of vacuolar (lysosomal) proteolytic function. The degradation of two other native ER proteins, Sec61p and Sec63p, normal components of the ER translocon, were also examined in parallel and found to be stabilized to some extent in HRD2- and UBC7-deficient strains. Together these findings attest to the remarkable mechanistic diversity in the normal degradation of ER proteins.

OBJECTIVE

To evaluate an innovative approach to maintaining physical, cognitive, and social functioning in frail, elderly nursing home residents at risk for transfer from a minimal care unit.

SUBJECTS/SETTING

Nineteen Russian-speaking residents of the Jewish Home in San Francisco who were newly enrolled in an on-site adult day care program.

METHODS

A formal evaluation of the program employed a repeated measures design with assessments at baseline and at Months 2, 3, 4, 6, and 9. Outcomes included stability of living situation, functional status, physical and mental health, cognitive functioning, sense of well-being and quality of life, and satisfaction with the program.

RESULTS

During this period, the cohort was medically stable and, although some evidenced cognitive decline, there was little change in their functional status. Nearly all of the residents reported improvement from baseline in some aspects of their lives, with the greatest proportions reporting positive changes in social support and quality of life.

CONCLUSIONS

Findings from this evaluation suggest that activities programming using the model described here may enhance the quality of life for some nursing home residents and enable them to remain in the least restrictive, as well as the least costly, living situation possible.

BACKGROUND

As part of a broader effort aimed at improving hospital safety, a large coalition of employers, the Leapfrog Group, will soon require hospitals caring for their employees to meet volume standards for 5 high-risk surgical procedures. We estimated the potential benefits of full nationwide implementation of these volume standards. METHODS. Using data from Nationwide Inpatient Sample and other sources, we first estimated the total number of each of the 5 procedures-coronary-artery bypass graft, abdominal aortic aneurysm repair, coronary angioplasty, esophagectomy, and carotid endarterectomy-performed each year in hospitals in US metropolitan areas. (Leapfrog exempts hospitals in rural areas to avoid access issues.) We then projected the effectiveness of volume standards (in terms of relative risks of mortality) for each procedure using data from a published structured literature review.

RESULTS

With full implementation nationwide, the Leapfrog volume standards would save 2581 lives. Of the procedures, volume standards would save the most lives with coronary-artery bypass graft (1486), followed by abdominal aortic-aneurysm repair (464), coronary angioplasty (345), esophagectomy (168), and carotid endarterectomy (118). In our estimates of the number of lives saved, we considered assumptions about how many patients would be affected and the effectiveness of volume standards (ie, strength of underlying volume-outcome relationships with each procedure).

CONCLUSIONS

If the Leapfrog volume standards are successfully implemented, employers and health-care purchasers could prevent many surgical deaths by requiring hospital volume standards for high-risk procedures.

The nuclear expression and action of the nuclear factor kappa B (NF-kappaB) transcription factor requires signal-coupled phosphorylation and degradation of the IkappaB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role. Our studies now demonstrate that the RelA subunit of NF-kappaB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IkappaBalpha. Acetylated RelA is subsequently deacetylated through a specific interaction with histone deacetylase 3 (HDAC3). This deacetylation reaction promotes effective binding to IkappaBalpha and leads in turn to IkappaBalpha-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)-dependent pathway. Deacetylation of RelA by HDAC3 thus acts as an intranuclear molecular switch that both controls the duration of the NF-kappaB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-kappaB-IkappaBalpha complexes.