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Biomedical subjects

N A Miller

Publications and source records attributed to N A Miller.

At least 19 recordsLinked to original sources

A novel activating function of c-Src and Stat3 on HGF transcription in mammary carcinoma cells.

In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by stromal cells, and stimulates in a paracrine manner epithelial cells expressing the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are frequently overexpressed, possibly establishing an autocrine HGF/Met loop that promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF expression in carcinoma cells are not known. We previously demonstrated a cooperative effect between c-Src and Stat3 in the activation of HGF transcription in mammary carcinoma cells. The present report defines a novel Stat3 consensus site at nt -95 in the HGF promoter that is highly conserved in human and mouse, and is required for c-Src and Stat3 to activate HGF transcription in breast epithelial cells. DNA-protein binding studies demonstrated high affinity binding of a Stat3-containing complex to the nt -95 site. Endogenous Stat3 binding to this region of the HGF promoter in carcinoma cells expressing HGF was demonstrated using a chromatin immunoprecipitation assay. In addition, coexpression of Stat3 and activated c-Src caused increased expression of endogenous HGF mRNA and protein and marked cell scattering in breast epithelial cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that regulates HGF promoter activity, and is linked to transformation of mammary epithelial cells.

Animals↗

Cross-hybridization of closely related genes on high-density macroarrays.

DNA macroarrays are used in many areas of molecular biology research for applications ranging from gene discovery to gene expression profiling. As an increasing number of specialized macroarrays containing genes related by function or pathway are becoming available, a question that needs to be addressed is the level of hybridization signal specificity between highly similar genes that can be achieved. We have examined the ability of our LifeGrid macroarrays to distinguish hybridization signals between closely related genes. We determined the level of cross-hybridization among genes ranging from 52% to 94% sequence identity. Fragments of genes fromfive protein families were arrayed onto nylonfilters. Thefilters were subsequently hybridized with a 33P-labeled probe prepared from a pool of synthetic mRNA transcripts containing a representative of each protein family. We found that fragments containing sequences with up to 94% sequence identity displayed relatively little cross-hybridization. We conclude that this macroarray system is very specific and that hybridization signals from closely related genes can be reliably measured.

Cloning, Molecular↗

Use of Medicaid 1915(c) home- and community-based care waivers to reconfigure state long-term care systems.

Since Congressional authorization in 1981, Medicaid 1915(c) home- and community-based care waivers have influenced states' efforts to transform their long-term care systems. In 1997, every state participated in the 1915(c) waiver program, while waiver expenditures, at $8.1 billion, represented 59.6 percent of all Medicaid community-based care expenditures. To explore state-level factors that appear related to these expenditures, the authors turn to a body of work on Medicaid resource allocation. They compare the influence of five factors--sociodemographic, supply, economic, programmatic, and political environment--on states' allocations to long-term care expenditures and 1915(c) waiver expenditures. The state economic environment was an important influence on total, as well as waiver expenditures. State regulation of long-term care supply demonstrated the most substantive relationship, increasing the share of dollars supporting 1915(c) waivers from 11.6 to 20.0 over the study period, all else equal.

Aged↗

Regeneration of bone graft donor sites.

When crestal volume is greatly insufficient for the placement of dental implants, bone grafting is usually the most reliable ridge augmentation procedure. The grafts are most often taken in parietal or mandibular symphysis regions. Though not too noticeable, it seems contra-indicated and even potentially dangerous to leave zones like the cranium to repair spontaneously. Guided bone regeneration techniques have shown their ability to regenerate new bone under difficult conditions in jaws. Their use in bone graft donor sites is simple and the results are consistent. This report shows that 2 types of resorbable membranes are equally as efficacious in terms of new-bone formation.

Adult↗

Trends and issues in the Medicaid 1915(c) waiver program.

Over the past 15 years, Medicaid 1915(c) home and community-based waivers have made a substantial contribution to States' efforts to transform their long-term care (LTC) systems from largely institutional to community-based systems. By 1997, every State had implemented a waiver program for at least some subgroups of individuals with disabilities, and expenditures increased from $3.8 million in 1982 to more than $8.1 billion in 1997. Emerging, as well as long-standing, policy issues related to the waiver program include concerns with access, variation in availability by disability group, State decisions related to the provision of community-based LTC, and evidence on effectiveness.

Community Health Services↗

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast.

BACKGROUND: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. METHODS: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. RESULTS: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate; P=.07, for multivariate) and initial presentation (P=.05, for univariate; P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. CONCLUSIONS: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.

Adult↗

Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation.

Increased dietary fat intake and rate of breast epithelial cell proliferation have each been associated with the development of breast cancer. The goal of this study was to measure the effect of a low fat, high carbohydrate diet on the rate of breast epithelial cell proliferation in women at high risk for breast cancer. Women were recruited from the intervention and control groups of a randomized low fat dietary intervention trial, breast epithelial cells were obtained by fine needle aspiration, and cell proliferation was assessed in these samples using immunofluorescent detection of Ki-67 and PCNA. The effects of needle size and study group on cell yield and cytologic features of the cells were also examined. Fifty three women (20 in the intervention group and 33 in the control group) underwent the biopsy procedure. Slides from 38 subjects were stained for Ki-67 and from 14 subjects for PCNA. No cell proliferation (fluorescence) was detected for either Ki-67 or PCNA in any of the slides. Epithelial cell yield and number of stromal fragments were greater with a larger needle size. Numbers of stromal fragments and bipolar naked nuclei were greater in the low fat as compared to the control group but no differences in epithelial cell yield were observed between the two groups. This study confirms that fine needle aspiration biopsy is a feasible method of obtaining epithelial cells from women without discrete breast masses, but suggests that cell proliferation cannot be assessed using Ki-67 and PCNA in such samples.

Biomarkers↗

Transforming the long-term care system: policy and managerial challenges.

As the need for long-term care of people with disabilities increases, the model of care faces crucial changes, including a shift from institutional to independent living, significant changeover in organizational auspices, and policies created by the Americans with Disabilities Act. Such systemic changes pose fiscal, technological, and social challenges to policymakers and managers of care delivery.

Persons with Disabilities↗

Patient centered long-term care.

Drawing upon an individual's needs, values, and expectations to guide decisionmaking and care giving is integral to long-term care (LTC). Articles in this issue demonstrate that client values and preferences can be elicited and used to guide decisionmaking about LTC. Service delivery and payment features can be shaped to support the patient/consumer, as well as to support and strengthen her or his informal caregivers. Significant constraints to making LTC more client centered are also identified. Key issues relate to the availability of and methods to process information as well as pressures on provider staff that impede their ability to support clients and their families. More broadly, access to appropriate LTC services is being shaped by programmatic shifts and legal forces that may enhance or impede the ability to place patients/clients at the center of LTC.

Activities of Daily Living↗

Joining forces to improve point-of-care testing.

Point-of-care (POC) testing takes a "laboratory" test directly to the patient's bedside. Although bedside testing is not new, the compliance standards are relatively new. Regulations ensure that all personnel are trained to properly perform the test. The central laboratory and nursing of this hospital merge the best skills of both units to create a successful POC testing program.

Cooperative Behavior↗

Squamous cell carcinoma of the breast.

OBJECTIVE: To review the mammographic and ultrasonographic features of primary breast cancer containing squamous cell carcinoma. PATIENTS AND METHODS: From medical records for breast cancer patients seen over a 37-year period the authors identified 19 patients with squamous cell carcinoma, for 5 of whom histologic sections and imaging studies were available. The tumours were classified on the basis of histologic findings as pure (in two patients) or predominantly (in three patients) squamous cell carcinoma. Mammograms were available for four of the patients, and the mammographic report only was available for analysis for the fifth. Ultrasonography had been performed for four of the patients; the images were available for two of the patients and the reports only for two. RESULTS: The median age of the patients was 55 years. The mean size of the tumours, all of which were palpable, was 5.0 cm. None of the tumours was connected to the skin, arose in the nipple-areolar complex or was metastatic. On mammography, the margins of all five masses, which were oval in shape, were indistinct and partly well-circumscribed; in three cases, the tumour margin was also partly spiculated. No malignant microcalcifications were seen. The two "pure" squamous cell carcinoma tumours appeared on ultrasonography as solid hypoechoic masses, and two of the predominantly squamous cell carcinoma tumours had both cystic and solid components. At gross pathological examination, four of the tumours (two "pure" and two predominantly squamous cell carcinoma) were cystic, which reflected areas of necrosis and cyst formation. CONCLUSION: Although "pure" or predominantly squamous cell carcinoma is a rare histologic variant of breast cancer that lacks any typical mammographic features, this tumour can be added to the differential diagnosis of cystic breast masses seen on ultrasonography.

Aged↗

A profile of home health users in 1992.

Recently, the use of home health services by Medicare beneficiaries has been growing. From 1987 to 1992, the percentage of all enrollees receiving home health rose from 4.8 to 7.2 percent, while the average number of visits among users increased from 23 to 54. This article uses the 1992 Medicare Current Beneficiary Survey (MCBS) to profile home health users. In addition to providing descriptive information about who uses Medicare home health, Tobit models are estimated to determine the factors that predict home health utilization and reimbursement. Various policy options for redesigning the home health benefit are also discussed.

Activities of Daily Living↗

The Medicare home health initiative.

This article describes the Medicare home health benefit and summarizes growth and change in the use of the benefit and in the industry providing home health care. The article also details the organization and goals of the Home Health Initiative, describes its four key components--quality assurance (QA), administration, policy, and research-and concludes with a discussion of the status of the Initiative.

Centers for Medicare and Medicaid Services, U.S.↗

[Evaluation of the Community Periodontal Index of Treatment Needs (CPITN)].

This article consists of a critical analysis of the CPITN, an index based on binary logic and the partial recording of data. The authors discuss the possible loss of information connected with the fact that the data collection covers 6 scores per individual instead of more comprehensive scoring for which there are methods involving several surfaces per tooth. This approach is discussed on the basis of research carried out by the authors and a review of the literature. Moreover, one aspect of the CPITN which often gives rise to controversy is whether recession is pathological or not, and therefore to what extent it should be recorded. This aspect is discussed and analysed. Finally, quantification of the time needed to provide periodontal care is also relevant when using this index, which is the reference index for the WHO Global Oral Data Bank.

Data Collection↗

The changing face of long-term care.

In this article, we present population estimates of individuals with disabilities and discuss the manner in which the composition of this population is changing. We then highlight aspects of service delivery systems that are evolving in response to the changing long-term care (LTC) population. Following a summary of financing issues, we discuss several cross-cutting issues related to the organization of service delivery, quality assurance (QA), and financing. Current and future Health Care Financing Administration (HCFA) research and demonstrations emerging from these issues are then described.

Chronic Disease↗

Qualitative analysis of the Program of All-inclusive Care for the Elderly (PACE).

The innovative model of capitated acute and chronic care for nursing-home-eligible elderly persons, which was developed at On Lok in San Francisco's Chinatown and stresses using community care in lieu of institutional care, has been replicated at eight sites around the country. The early experience in developing these sites tests the extent to which the principles of this approach, based on day health care, can be reproduced in a variety of other settings. Four of the eight sites have begun formal capitated care; enrollment has been less active than anticipated, apparently due to reluctance to change physicians and resistance to day care.

Acute Disease↗

Medicaid 2176 home and community-based care waivers: the first ten years.

Budget reconciliation legislation in 1981 created a waiver program whereby states could provide home and community-based care under Medicaid for certain populations. States spent nearly $1.7 billion on services delivered under these waivers, known as 2176 waivers, in 1991, compared with $3.8 million in 1982, when only six states were participating in the program. Although these programs have not been rigorously evaluated for effectiveness, they continue to be a popular approach to delivering care outside of institutions for various groups. Across all states, states spent 13.4 percent of their Medicaid long-term care dollars on care outside of institutions (which includes the 2176 waiver program).

Community Health Services↗

An evaluation of substance misuse treatment providers used by an employee assistance program.

Structural measures of access, continuity, and quality of substance misuse treatment services were compared in 30 fee-for-service (FFS) facilities and nine health maintenance organizations (HMOs). Probit models related effects of the provider system (FFS or HMO) and the system's structural characteristics to 243 employees' access to and outcomes from treatment. Access was decreased in Independent Practice Association (IPA)/network HMOs and in all facilities which did not employ an addictionologist or provide coordinated treatment services. When bivariate correlations were examined, both use of copayments and imposing limits to the levels of treatment covered were negatively related to access, while a facility's provision of ongoing professional development was positively associated with access. These correlations did not remain significant in the multivariate probits. Receiving treatment in a staff model HMO and facing limits to the levels of treatment covered were negatively associated with attaining sufficient progress, while receiving treatment in a facility which provided ongoing professional development was positively related to progress: these effects did not remain significant in multivariate analyses. Implications for employee assistance program (EAP) staff in their role as case managers and for EAP staff and employers in their shared role as purchasers of treatment are discussed.

Adult↗